WorldWideScience

Sample records for penicillin g

  1. Penicillin G Procaine Injection

    Science.gov (United States)

    Penicillin G procaine injection is used to treat certain infections caused by bacteria. Penicillin G procaine injection should not be used to ... early in the treatment of certain serious infections. Penicillin G procaine injection is in a class of ...

  2. 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. ...

  3. 21 CFR 522.1696a - Penicillin G benzathine and penicillin G procaine suspension.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G benzathine and penicillin G procaine... FORM NEW ANIMAL DRUGS § 522.1696a Penicillin G benzathine and penicillin G procaine suspension. (a) Specifications. Each milliliter of aqueous suspension contains penicillin G benzathine and penicillin G procaine...

  4. 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.

  5. 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...

  6. 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 ...

  7. 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...

  8. 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...

  9. 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 ...

  10. 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...

  11. Pertraction of Penicillin G in Hollow Fiber Contained Liquid Membranes

    International Nuclear Information System (INIS)

    Miesiac, I.; Szymanowski, J.

    1998-01-01

    Pertraction of Penicillin G in Hollow Fiber Contained Liquid Membranes was investigated in a system consisting of 2 Liqui Cel 106 modules from Hoechst Celanese. The flux of Pen G depended upon the content of n-octanol and of Amberlite LA2 in kerosene used as a membrane phase. During the pertraction of Pen G in HFCLM system the pH difference between the both buffered aqueous phases diminished proportionally to the contact time with the membrane phase. The flux of citric acid used as a buffer component in the feed phase attained 11.8 mM/m 2 x h and was comparable with the flux of Pen G equal to 18.4 mM/m 2 x h. In order to eliminate the undesired transport of citric acid, CO 2 was used as a volatile buffer component. Although the pH values were stabilised in the range of 5.47 and 7.45 in the feed and strip phase, respectively, the achieved Pen G flux was significantly lower. (author)

  12. 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...

  13. 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. ...

  14. 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.

  15. 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...

  16. 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...

  17. 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

  18. 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.

  19. 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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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.

  4. 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 ...

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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...

  10. 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

  11. 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...

  12. 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

  13. 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

  14. 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

  15. SERS Detection of Penicillin G Using Magnetite Decorated with Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    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.

  16. 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

  17. 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.

  18. A SIMULATION OF THE PENICILLIN G PRODUCTION BIOPROCESS APPLYING NEURAL NETWORKS

    Directory of Open Access Journals (Sweden)

    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

  19. A new insight about pharmaceutical dosage forms for benzathine penicillin G

    Directory of Open Access Journals (Sweden)

    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.

  20. Covalent immobilization of penicillin G acylase on aminopropyl-functionalized mesostructured cellular foams.

    Science.gov (United States)

    Zhao, Junqi; Wang, Yujun; Luo, Guangsheng; Zhu, Shenlin

    2010-10-01

    Mesostructured cellular foams (MCFs) are suitable for biomolecular immobilization because of their relatively large-pore diameter and pore volume. Penicillin G acylase (PGA) was immobilized on aminopropyl-functionalized MCFs through Schiff base reaction. It is shown that PGA could be fixed more firmly through the covalent immobilization on aminopropyl-functionalized MCFs support than through the adsorption immobilization on blank MCFs. The PGA loading amount on the aminopropyl-functionalized MCFs could reach 443 mg/g (dry support), and the apparent activity could achieve up to 4138 U/g (dry support). The influence of the amount of grafted aminopropyl group was studied, and it is found that the optimal molar ratio of MCFs to APTS was 15/1; in addition, the suitable enzyme distribution density for the specific activity of the immobilized PGA was 0.7 mg enzyme per m(2) of specific area of MCFs. Copyright 2010 Elsevier Ltd. All rights reserved.

  1. Epoxy-functionalized mesostructured cellular foams as effective support for covalent immobilization of penicillin G acylase

    Science.gov (United States)

    Xue, Ping; Xu, Fang; Xu, Lidong

    2008-12-01

    The epoxy-functionalized mesoporous cellular foams (G-MCFs) with high specific surface area (˜400 m 2/g) and large-size mesopores (˜17 nm) were obtained by condensation of 3-glycidoxypropyltriethoxysilane (GPTS) and the surface silanol groups of mesoporous cellular foams (MCFs) and used as the support for immobilization of penicillin G acylase (PGA). The structural properties of G-MCF were characterized by FT-IR, N 2 adsorption, TG-DTA and 29Si MAS NMR. The studies indicated that the glycidoxypropyl groups were chemically bonded to the silicon atoms on the surface of MCF. The epoxy-functionalized mesoporous cellular foams can provide the microenvironments suitable for the immobilization of PGA, and the enzyme molecules could be immobilized covalently onto the G-MCF under mild conditions by reaction between the amino groups of the enzyme molecules and the epoxy groups on the surface of G-MCF. The PGA immobilized on G-MCF (PGA/G-MCF) exhibited the apparent activity of 1782 IU/g and 46.6% of activity recovery for hydrolyzing penicillin G potassium to produce 6-aminopenicillanic acid at 37 °C which were higher than that of PGA on pure silica MCF (1521 IU/g and 39.8%, respectively). The kinetic study also indicated that PGA immobilized on G-MCF has a Km of 2.1 × 10 -2 mol/L lower than that of PGA immobilized on the pure silica MCF (5.0 × 10 -2 mol/L). These may be attributed to the enhanced surface affinity between G-MCF support and the substrate molecules. Due to the covalent immobilization of PGA molecules on the surface of G-MCF, the immobilized PGA with considerable operational stability was achieved. The activity of PGA/G-MCF is still about 91.4% of its initial activity at the 10th cycle reuse while that of PGA/MCF only remains 41.5% of its initial activity at the same reuse numbers. In addition, the investigation results show the thermal stability and durability on acid or basic medium of PGA immobilized on G-MCF were improved remarkably.

  2. Epoxy-functionalized mesostructured cellular foams as effective support for covalent immobilization of penicillin G acylase

    International Nuclear Information System (INIS)

    Xue Ping; Xu Fang; Xu Lidong

    2008-01-01

    The epoxy-functionalized mesoporous cellular foams (G-MCFs) with high specific surface area (∼400 m 2 /g) and large-size mesopores (∼17 nm) were obtained by condensation of 3-glycidoxypropyltriethoxysilane (GPTS) and the surface silanol groups of mesoporous cellular foams (MCFs) and used as the support for immobilization of penicillin G acylase (PGA). The structural properties of G-MCF were characterized by FT-IR, N 2 adsorption, TG-DTA and 29 Si MAS NMR. The studies indicated that the glycidoxypropyl groups were chemically bonded to the silicon atoms on the surface of MCF. The epoxy-functionalized mesoporous cellular foams can provide the microenvironments suitable for the immobilization of PGA, and the enzyme molecules could be immobilized covalently onto the G-MCF under mild conditions by reaction between the amino groups of the enzyme molecules and the epoxy groups on the surface of G-MCF. The PGA immobilized on G-MCF (PGA/G-MCF) exhibited the apparent activity of 1782 IU/g and 46.6% of activity recovery for hydrolyzing penicillin G potassium to produce 6-aminopenicillanic acid at 37 o C which were higher than that of PGA on pure silica MCF (1521 IU/g and 39.8%, respectively). The kinetic study also indicated that PGA immobilized on G-MCF has a K m of 2.1 x 10 -2 mol/L lower than that of PGA immobilized on the pure silica MCF (5.0 x 10 -2 mol/L). These may be attributed to the enhanced surface affinity between G-MCF support and the substrate molecules. Due to the covalent immobilization of PGA molecules on the surface of G-MCF, the immobilized PGA with considerable operational stability was achieved. The activity of PGA/G-MCF is still about 91.4% of its initial activity at the 10th cycle reuse while that of PGA/MCF only remains 41.5% of its initial activity at the same reuse numbers. In addition, the investigation results show the thermal stability and durability on acid or basic medium of PGA immobilized on G-MCF were improved remarkably.

  3. Epoxy-functionalized mesostructured cellular foams as effective support for covalent immobilization of penicillin G acylase

    Energy Technology Data Exchange (ETDEWEB)

    Xue Ping [Key Laboratory of Energy Resources and Chemical Engineering, Ningxia University, Yinchuan 750021 (China)], E-mail: Ping@nxu.edu.cn; Xu Fang [Department of Molecule Biology, Ningxia Medical College, Yinchuan 750021 (China); Xu Lidong [Key Laboratory of Energy Resources and Chemical Engineering, Ningxia University, Yinchuan 750021 (China)

    2008-12-30

    The epoxy-functionalized mesoporous cellular foams (G-MCFs) with high specific surface area ({approx}400 m{sup 2}/g) and large-size mesopores ({approx}17 nm) were obtained by condensation of 3-glycidoxypropyltriethoxysilane (GPTS) and the surface silanol groups of mesoporous cellular foams (MCFs) and used as the support for immobilization of penicillin G acylase (PGA). The structural properties of G-MCF were characterized by FT-IR, N{sub 2} adsorption, TG-DTA and {sup 29}Si MAS NMR. The studies indicated that the glycidoxypropyl groups were chemically bonded to the silicon atoms on the surface of MCF. The epoxy-functionalized mesoporous cellular foams can provide the microenvironments suitable for the immobilization of PGA, and the enzyme molecules could be immobilized covalently onto the G-MCF under mild conditions by reaction between the amino groups of the enzyme molecules and the epoxy groups on the surface of G-MCF. The PGA immobilized on G-MCF (PGA/G-MCF) exhibited the apparent activity of 1782 IU/g and 46.6% of activity recovery for hydrolyzing penicillin G potassium to produce 6-aminopenicillanic acid at 37 {sup o}C which were higher than that of PGA on pure silica MCF (1521 IU/g and 39.8%, respectively). The kinetic study also indicated that PGA immobilized on G-MCF has a K{sub m} of 2.1 x 10{sup -2} mol/L lower than that of PGA immobilized on the pure silica MCF (5.0 x 10{sup -2} mol/L). These may be attributed to the enhanced surface affinity between G-MCF support and the substrate molecules. Due to the covalent immobilization of PGA molecules on the surface of G-MCF, the immobilized PGA with considerable operational stability was achieved. The activity of PGA/G-MCF is still about 91.4% of its initial activity at the 10th cycle reuse while that of PGA/MCF only remains 41.5% of its initial activity at the same reuse numbers. In addition, the investigation results show the thermal stability and durability on acid or basic medium of PGA immobilized on G

  4. 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.

  5. 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...

  6. Penicillin Allergy

    Science.gov (United States)

    ... Seizures Loss of consciousness Other conditions resulting from penicillin allergy Less-common penicillin allergy reactions occur days ... immune system to create an antibody to it. Penicillins and related drugs Penicillins belong to a class ...

  7. 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.

  8. 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...

  9. Evaluation of penicillin G residues by kidney inhibition swab tests in sow body fluids and tissues following intramuscular injection

    Science.gov (United States)

    In 2011, the USDA-Food Safety and Inspection Service (FSIS) changed the method used for screening swine tissues for antimicrobial residues from the Fast Antimicrobial Screen Test to the Kidney Inhibition Swab (KIS(TM)). Here, we describe the use of KIS(TM) test for the detection of penicillin G res...

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

    Science.gov (United States)

    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...

  11. 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,

  12. 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...

  13. Stabilization of penicillin G acylase by immobilization on glutaraldehyde-activated chitosan

    Directory of Open Access Journals (Sweden)

    W. S. Adriano

    2005-12-01

    Full Text Available The objective of this work was to study enzyme immobilization on chitosan activated with glutaraldehyde, aiming to produce a cheap biocatalyst. Two different immobilization strategies were studied: one-point and multipoint covalent attachment to the solid matrix. The multipoint covalent attachment derivative had an 82% immobilization yield. It was 4.9-fold more stable than the free enzyme at 50°C and 4.5-fold more stable than soluble enzyme at pH 10.0. The one-point derivative had an 85% immobilization yield. It was 2.7-fold more stable than the free enzyme at 50°C and 3.8-fold more stable than soluble PGA at pH 10.0. Results indicated that chitosan can be loaded with PGA above 330 IU/g. Intraparticle diffusive effects, however, limited hydrolysis of penicillin G catalyzed by those derivatives at 37°C and 25°C. Operational stability assays were performed and the multipoint derivative exhibited a half-life of 40 hours.

  14. 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.

  15. 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.

  16. 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.

  17. 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%).

  18. A Proposal for Six Sigma Integration for Large-Scale Production of Penicillin G and Subsequent Conversion to 6-APA

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 21 CFR 558.460 - Penicillin.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin. 558.460 Section 558.460 Food and Drugs... Animal Feeds § 558.460 Penicillin. (a) Specifications. As penicillin procaine G or feed grade penicillin.... (1) It is used as follows: Penicillin in grams per ton Combination in grams per ton Indications for...

  5. 21 CFR 520.1696a - Buffered penicillin powder, penicillin powder with buffered aqueous diluent.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Buffered penicillin powder, penicillin powder with... FORM NEW ANIMAL DRUGS § 520.1696a Buffered penicillin powder, penicillin powder with buffered aqueous diluent. (a) Specifications. When reconstituted, each milliliter contains penicillin G procaine equivalent...

  6. [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%.

  7. The effect of subminimal inhibitory concentrations of penicillin on growth rate and haemolysin activity of group G Streptococcus

    Directory of Open Access Journals (Sweden)

    Verônica V. Vieira

    1993-09-01

    Full Text Available The influence of the subminimal inhibitory concentrations (1/3 and 1/4 of the MIC of penicillin on growth rate and on haemolysin production of a strain of group G Streptococcus was studied. It was shown that 1/3 of the MIC almost completely inhibited the bacterial growth, but it was not able to inhibit haemolysin activity in the culture supernate. The generation time of bacteria grown in 1/4 of the MIC was approximately twice longer than that of the control culture. In all cultures, the haemolysin, after being produced (or liberated, reached a peak and decreased to low levels, which could suggest that group G Streptococcus produces some end products of metabolism that are able to inhibit haemolysin activity.

  8. Hitler's penicillin.

    Science.gov (United States)

    Wainwright, Milton

    2004-01-01

    During the Second World War, the Germans and their Axis partners could only produce relatively small amounts of penicillin, certainly never enough to meet their military needs; as a result, they had to rely upon the far less effective sulfonamides. One physician who put penicillin to effective use was Hitler's doctor, Theodore Morell. Morell treated the Führer with penicillin on a number of occasions, most notably following the failed assassination attempt in July 1944. Some of this penicillin appears to have been captured from, or inadvertently supplied by, the Allies, raising the intriguing possibility that Allied penicillin saved Hitler's life.

  9. 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

    Biofilms are microbial aggregates that show high tolerance to antibiotic treatments in vitro and in vivo. Killing and removal are both important in biofilm control, therefore methods that measure these two mechanisms were evaluated in a parallel experimental design. Kill was measured using the single tube method (ASTM method E2871) and removal was determined by video microscopy and image analysis using a new treatment flow cell. The advantage of the parallel test design is that both methods used biofilm covered coupons harvested from a CDC biofilm reactor, a well-established and standardized biofilm growth method. The control Staphylococcus aureus biofilms treated with growth medium increased by 0·6 logs during a 3-h contact time. Efficacy testing showed biofilms exposed to 400 μmol l -1 penicillin G decreased by only 0·3 logs. Interestingly, time-lapse confocal scanning laser microscopy revealed that penicillin G treatment dispersed the biofilm despite being an ineffective killing agent. In addition, no biofilm removal was detected when assays were performed in 96-well plates. These results illustrate that biofilm behaviour and impact of treatments can vary substantially when assayed by different methods. Measuring both killing and removal with well-characterized methods will be crucial for the discovery of new anti-biofilm strategies. Biofilms are tolerant to antimicrobial treatments and can lead to persistent infections. Finding new anti-biofilm strategies and understanding their mode-of-action is therefore of high importance. Historically, antimicrobial testing has focused on measuring the decrease in viability. While kill data are undeniably important, measuring biofilm disruption provides equally useful information. Starting with biofilm grown in the same reactor, we paired assessment of biofilm removal using a new treatment-flow-cell and real-time microscopy with kill data collected using the single tube method (ASTM E2871). Pairing these two methods

  10. 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

  11. Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia : Effects of continued penicillin prophylaxis

    NARCIS (Netherlands)

    Bjornson, AB; Falletta, JM; Verter, JI; Buchanan, GR; Miller, ST; Pegelow, CH; Iyer, RV; Johnstone, HS; DeBaun, MR; Wethers, DL; Woods, GM; Holbrook, CT; Becton, DL; Kinney, TR; Reaman, GH; Kalinyak, K; Grossman, NJ; Vichinsky, E; Reid, CD

    1996-01-01

    Objectives: (1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years ski children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses. Study design:

  12. 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)

    Sows (n=126) were administered penicillin G procaine at 5x the label dose for 3 consecutive days. Eighteen sows were slaughtered on each withdrawal days, 5, 10, 15, 20, 25, 32, or 39 d after treatment. Urine samples were collected at slaughter and were frozen at -80 °C until screening as positive ...

  13. 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.

  14. 60Co-irradiation as an alternate method for sterilization of penicillin G, neomycin, novobiocin, and dihydrostreptomycin

    International Nuclear Information System (INIS)

    Tsuji, K.; Rahn, P.D.; Steindler, K.A.

    1983-01-01

    The effects of the use of 60Co-irradiation to sterilize antibiotics were evaluated. The antibiotic powders were only occasionally contaminated with microorganisms. The D-values of the products and environmental isolates were 0.028, 0.027, 0.015, 0.046, 0.15, 0.018, and 0.19 Mrads for Aspergillus species (UC 7297, 7298), A. fumigatus (UC 7299), Rhodotorula species (UC 7300), Penicillium oxalicum (UC 7269), Pseudomonas maltophilia (UC 6855), and a biological indicator microorganism, Bacillus pumilus spores (ATCC 27142). An irradiation dose of 1.14 Mrads, therefore, was sufficient to achieve a six-log cycle destruction of B. pumilus spores. Based on the bioburden data, a minimum irradiation dose of 1.05 Mrads was calculated to be sufficient to obtain a 10(-6) probability of sterilizing the most radioresistant isolate, Pen. oxalicum. To determine the radiolytic degradation scheme and the stability of the antibiotics following irradiation, high-performance liquid chromatographic (HPLC) methods were developed. The resulting rates of degradation for the antibiotics were 0.6, 1.2, 2.3, and 0.95%/Mrad for penicillin G, neomycin, novobiocin, and dihydrostreptomycin, respectively. Furthermore, radiolytic degradation pathways for the antibiotics were identified and found to be similar to those commonly encountered when antibiotics are subjected to acidic, basic, hydrolytic, or oxidative treatments. No radiolytic compounds unique to 60Co-irradiation were found

  15. In situ one-pot preparation of superparamagnetic hydrophilic porous microspheres for covalently immobilizing penicillin G acylase to synthesize amoxicillin

    Science.gov (United States)

    Xue, Ping; Gu, Yaohua; Su, Weiguang; Shuai, Huihui; Wang, Julan

    2016-01-01

    Magnetic hydrophilic porous microspheres were successfully one-pot synthesized for the first time via in situ inverse suspension polymerization of glycidyl methacrylate, N,N‧-methylene bisacrylamide and 2-hydroxyethyl methacrylate in the presence of Fe3+ and Fe2+ dispersed in formamide, which were denoted as magnetic Fe3O4-GMH microspheres. The morphology and properties of magnetic Fe3O4-GMH microspheres were characterized by SEM, VSM, XRD, FTIR, and so on. The formamide content had an important influence on the morphology of Fe3O4-GMH, and nearly perfectly spherical Fe3O4-GMH particles were formed when the amount of formamide was 15 ml. The diameters of the microspheres were in the range of 100-200 μm and Fe3O4-GMH exhibited superparamagnetic behavior with the saturation magnetization of 5.44 emu/g. The specific surface area of microspheres was 138.7 m2/g, the average pore diameter and pore volume were 15.1 nm and 0.60 cm3/g, respectively. The content of oxirane groups on Fe3O4-GMH was 0.40 mmol/g. After penicillin G acylase (PGA) was covalently immobilized on Fe3O4-GMH microspheres, the catalytic performance for amoxicillin synthesis by 6-aminopenicillanic acid and D-hydroxyphenylglycine methyl ester was largely improved. As a result, 90.1% amoxicillin yield and 1.18 of the synthesis/hydrolysis (S/H) ratio were achieved on PGA/Fe3O4-GMH with ethylene glycol as solvent, but only 62.6% amoxicillin yield and 0.37 of the S/H ratio were obtained on free PGA under the same reaction conditions. Furthermore, the amoxicillin yield and S/H ratio were still kept at 88.2% and 1.06, respectively after the immobilized PGA was magnetically separated and recycled for 10 times, indicating that PGA/Fe3O4-GMH had a very good reusability.

  16. 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.

  17. Radioiododestannylation. Convenient synthesis of a stable penicillin derivative for rapid penicillin binding protein (PBP) assay

    International Nuclear Information System (INIS)

    Blaszczak, L.C.; Halligan, N.G.; Seitz, D.E.

    1989-01-01

    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. The structure and penicillin binding protein (PBP) affinity of p-[ 125 I]-penicillin V (IPV) are similar to penicillin G and the product can be used directly without purification in the PBP assay. Because of the high degree of stability toward autoradiolysis and equivalent PBP binding affinity, IPV can be used in place of [ 3 H]-penicillin G or [ 14 C]-penicillin G for these experiments. (author)

  18. 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.

  19. 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

  20. 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...

  1. Stability of penicillin G sodium diluted with 0.9% sodium chloride injection or 5% dextrose injection and stored in polyvinyl chloride bag containers and elastomeric pump containers.

    Science.gov (United States)

    Hossain, Mirza Akram; Friciu, Mihaela; Aubin, Sebastien; Leclair, Grégoire

    2014-04-15

    The stability of penicillin G sodium solutions stored in polyvinyl chloride (PVC) bags or elastomeric pump containers was studied. Test samples were prepared by diluting powdered penicillin G sodium (10 million units/10-mL vial) to solutions of 2,500 or 50,000 units/mL with 0.9% sodium chloride injection or 5% dextrose injection. The preparations were transferred to 250-mL PVC bags and elastomeric pump containers. All samples were prepared in triplicate and stored at 5°C. Chemical stability was measured by a stability-indicating high-performance liquid chromatographic (HPLC) assay and by pH evaluation. Particulate matter was evaluated according to compendial standards using a light-obscuration particle count test. Preparations were visually examined throughout the study. After 21 days of storage, all test samples remained chemically stable, with an HPLC assay recovery value of more than 90% of the initial value. After 28 days, all samples prepared with either diluent and stored in PVC bags, as well as the samples diluted to 2,500 units/mL with sodium chloride injection and stored in elastomeric pump containers, did not meet the recovery acceptance limit. For all test samples, the mean pH consistently decreased during storage, from about 6.4 to about 5.5. Particle counts remained acceptable throughout the study, and no change in appearance was observed. Penicillin G for injection (2,500 and 50,000 units/mL) diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored at 5°C in PVC containers or elastomeric pump containers was physically and chemically stable for a period of at least 21 days.

  2. Penicillin-resistant viridans streptococci have obtained altered penicillin-binding protein genes from penicillin-resistant strains of Streptococcus pneumoniae.

    OpenAIRE

    Dowson, C G; Hutchison, A; Woodford, N; Johnson, A P; George, R C; Spratt, B G

    1990-01-01

    Penicillin-resistant strains of Streptococcus pneumoniae possess altered forms of penicillin-binding proteins (PBPs) with decreased affinity for penicillin. The PBP2B genes of these strains have a mosaic structure, consisting of regions that are very similar to those in penicillin-sensitive strains, alternating with regions that are highly diverged. Penicillin-resistant strains of viridans groups streptococci (e.g., S. sanguis and S. oralis) that produce altered PBPs have also been reported. ...

  3. 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.

  4. 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.

  5. 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.

  6. Effects of tiamulin, neomycin, tetracycline, fluorophenicol, penicillin G, Linco-Spectin, erythromycin and oxytetracycline on controlling bacterial contaminations of the river buffalo (Buballus bubalis) semen.

    Science.gov (United States)

    Alavi-Shoushtari, S M; Ahmadi, M; Shahvarpour, S; Kolahian, S

    2007-09-15

    In order to investigate the effects of tiamulin, neomycin, tetracycline, fluorophenicol, penicillin G, Linco-Spectin (0.15 mg mL(-1) lincomycin + 0.3 mg mL(-1) spectinomycin), erythromycin and oxytetracycline on controlling bacterial contaminations of the river buffalo semen, 120 mL diluted buffalo bull semen (diluted by tris-egg yolk extender) was divided into 5 mL tubes after initial evaluation and before (control sample) and at 0, 2, 6, 12 and 24 h after adding each of the above antibiotics at the recommended dose (D) and twice the recommended dose (Dx2) to the semen samples, each sample was cultured 4 times on Muller-Hinton agar medium and the results were recorded after 18 h incubation at 37 degrees C. Tiamulin, tetracycline, neomycin and fluorophenicol were ineffective. Oxytetracycline was effective in both D and Dx2 (p < 0.001). Penicillin G in both D and Dx2 was effective (p < 0.001). Linco-Spectin was effective, though not significant, in D at 2 h and in Dx2 at 0 h only. Erythromycin in D was not significantly effective, but, in Dx2 was effective (p < 0.001). Duration of the antibiotic exposure had no significant effect on the antibiotic potentials except for Linco-Spectin at 2 h (p < 0.014). The biochemical tests identified the contaminant bacteria as being a member of Arcanobacter (Corynebacterium) sp. In the next step, the semen sample of the same bull was taken, semen quality tests were carried out and the semen was diluted with the same extender (tris-egg yolk) + 7% glycerol, containing a double dose (Dx2) of these antibiotics and semen quality tests were carried out immediately after dilution, 18 h after storage at 4 degrees C and after the semen was packed in the straws, frozen in liquid nitrogen (-196 degrees C) and later thawed in 37 degrees C water bath to investigate whether these antibiotics have any adverse effect on the spermatozoa during the process of freezing and thawing. The comparison of the results with those of the control group (the

  7. Using a medium of free amino acids to produce penicillin g acylase in fed-batch cultivations of Bacillus megaterium ATCC 14945

    Directory of Open Access Journals (Sweden)

    R. G. Silva

    2006-03-01

    Full Text Available The production of penicillin G acylase (PGA, an important industrial enzyme from a wild strain of Bacillus megaterium using a pool of free amino acids as substrate was studied in a bench-scale bioreactor. Experiments carried out in shakers showed that the substitution of casein for free amino acids in the presence of cheese whey was the culture medium that provided the highest productivity. Several cultivations were carried out in a bioreactor operated in either batch or fed-batch mode. Batch runs showed that enzyme production is associated with microorganism growth. The following set of amino acids was preferentially consumed: Ala, Arg, Asp, Gly, Lys, Ser, Thr and Trp. On the other hand, the rates of consumption of His, Ile, Leu, Met, Phe, Pro, Tyr and Val were lower.

  8. 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 ...

  9. 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

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

    Science.gov (United States)

    Xue, Ping; Su, Weiguang; Gu, Yaohua; Liu, Haifeng; Wang, Julan

    2015-03-01

    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.

  11. 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 ...

  12. 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.

  13. 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...

  14. 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...

  15. 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.

  16. Comparing a combination of penicillin G and gentamicin to a combination of clindamycin and amikacin as prophylactic antibiotic regimens in prevention of clean contaminated wound infections in cancer surgery

    International Nuclear Information System (INIS)

    El-Mahallawy, H.A.; Hassan, S.Sh.; Khalifa, H.I.; Safa, M.M.E.; Khafagy, M.M.

    2013-01-01

    Background and aim: Appropriate antibiotic selection and timing of administration for prophylaxis are crucial to reduce the likelihood of surgical site infection (SSI) after a clean contaminated cancer surgery. Our aim is to compare the use of two prophylactic antibiotic (PA) regimens as regards efficacy, timing, and cost. Patients and methods: Two hundred patients with gastric, bladder, or colorectal cancer were randomized to receive preoperative PA, group A received penicillin G sodium and gentamicin and group B received clindamycin and amikacin intravenously. The demographic data of patients were collected, and they were observed for wound infections. Results: Infected wounds occurred in 19 patients with a rate of 9.5%. Highest incidence of SSI was among bladder cancer patients (14.2%); p = 0.044. The rate of SSI was 11 % in group A, and 8% in group B, p = 0.469. The cost of PA administered in group A was significantly less than that of group B (21.96 ± 3.22 LE versus 117.05 ± 12.74 LE, respectively; p < 0.001). SSI tended to be higher among those who had longer time for antibiotic and incision (≥ 30 min) than those who had shorter time interval (<30 min), (13% vs. 6.5%, respectively). Conclusion: Both penicillin + gentamicin and clindamycin + amikacin are safe and effective for the prevention of SSI in clean contaminated operative procedures. In a resource limited hospital, a regimen including penicillin + gentamicin is a cost-effective alternative for the more expensive and broader coverage of clindamycin + amikacin. Timing of PA is effective in preventing SSIs when administered 30 min before the start of surgery

  17. 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...

  18. Spectroscopic, Elemental and Thermal Analysis, and Positron Annihilation Studies on Ca(II), Sr(II), Ba(II), Pb(II), and Fe(III) Penicillin G Potassium Complexes

    Science.gov (United States)

    Refat, M. S.; Sharshara, T.

    2015-11-01

    The [Pb(Pin)2] · 3H2O, [M(Pin)(H2O)2(Cl)] · nH2O (M = SrII, CaII or BaII; n = 0-1), and [Fe(Pin)2(Cl)(H2O)] · H2O penicillin G potassium (Pin) complexes were synthesized and characterized using elemental analyses, molar conductivity, thermal analysis and electronic spectroscopy techniques. The positron annihilation lifetime (PAL) and Doppler broadening (DB) techniques have been employed to probe the defects and structural changes of Pin ligand and its complexes. The PAL and DB line-shape parameters were discussed in terms of the structure, molecular weight, ligand-metal molar ratio, and other properties of the Pin complexes.

  19. 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

  20. 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,

  1. 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

  2. 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....

  3. [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.

  4. 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.

  5. Réponse des différents taxons méiofaunistiques à la contamination par un antibiotique (la Penicilline G) : étude microcosmique.

    OpenAIRE

    Nasri, A.; Boufahja, F.; Hedfi, A.; Mahmoudi, E.; Aissa, P.; Essid, N.

    2013-01-01

    Une étude microcosmique a été réalisée pour déterminer l’effet d’un antibiotique (la Pénicilline G) sur une communauté méiofaunistique prélevée au niveau des sédiments de la lagune de Bizerte (Nord de la Tunisie).Cinq doses croissantes de ce contaminant émergent (D1 : 3 mg.L-1, D2 : 30 mg. L-1, D3 : 300 mg. L-1, D4 : 600 mg. L-1 et D5 : 700 mg. L-1), ont été mises en examen pendant 30 jours d’exposition. Les densités méiofaunistiques moyennes ont été très fluctuantes en comparant les microcos...

  6. 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.)

  7. 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...

  8. 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.

  9. 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

  10. 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...

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

    Science.gov (United States)

    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.

  12. 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.

  13. Penicillin-sensitive Moraxella prosthetic endocarditis. Near disaster caused by failure to treat with penicillin.

    OpenAIRE

    Chen, W; Lee, P K; Chau, P Y

    1982-01-01

    A patient with late prosthetic endocarditis resulting from Moraxella non-liquefaciens is reported. Correct laboratory indentification is of therapeutic importance as Moraxella is often highly sensitive to penicillin. Because of suspected penicillin sensitivity, antibiotics other than penicillin were used, but failed to control the endocarditis. Prompt response occurred when penicillin was given. Penicillin remains by far the most effective antibiotic for the treatment of endocarditis, particu...

  14. 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)

  15. 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...

  16. Penicillin skin testing in the evaluation and management of penicillin allergy.

    Science.gov (United States)

    Fox, Stephanie; Park, Miguel A

    2011-01-01

    to review the role of penicillin skin testing in the evaluation and management of penicillin allergy mediated by IgE. PubMed and OVID search of English-language articles regarding penicillin allergy, penicillin allergy testing, and management of penicillin allergy. articles pertinent to the subject matter were selected and reviewed. the major determinant (benzylpenicillin polylysine) detects the greatest number of penicillin allergic patients during skin testing, and the minor determinants of penicillin increase the sensitivity of penicillin skin testing. Penicillin skin testing to the major and minor determinants was found to have a negative predictive value of 97% to 99%. The incidence of systemic adverse reaction to penicillin skin testing is less than 1%. a detailed history of the prior reaction to penicillin is an integral part of the evaluation, but it is not accurate in predicting a positive penicillin skin test result. A patient with a negative penicillin skin test result to the major and minor determinants is at a low risk of an immediate-type hypersensitivity reaction to penicillin. Patients with a positive skin test result should undergo desensitization to penicillin or an alternative antibiotic should be considered.

  17. 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.

  18. 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

  19. In vivo kinetic analysis of the penicillin biosynthesis pathway using PAA stimulus response experiments.

    Science.gov (United States)

    Deshmukh, Amit T; Verheijen, Peter J T; Maleki Seifar, Reza; Heijnen, Joseph J; van Gulik, Walter M

    2015-11-01

    In this study we combined experimentation with mathematical modeling to unravel the in vivo kinetic properties of the enzymes and transporters of the penicillin biosynthesis pathway in a high yielding Penicillium chrysogenum strain. The experiment consisted of a step response experiment with the side chain precursor phenyl acetic acid (PAA) in a glucose-limited chemostat. The metabolite data showed that in the absence of PAA all penicillin pathway enzymes were expressed, leading to the production of a significant amount of 6-aminopenicillanic acid (6APA) as end product. After the stepwise perturbation with PAA, the pathway produced PenG within seconds. From the extra- and intracellular metabolite measurements, hypotheses for the secretion mechanisms of penicillin pathway metabolites were derived. A dynamic model of the penicillin biosynthesis pathway was then constructed that included the formation and transport over the cytoplasmic membrane of pathway intermediates, PAA and the product penicillin-G (PenG). The model parameters and changes in the enzyme levels of the penicillin biosynthesis pathway under in vivo conditions were simultaneously estimated using experimental data obtained at three different timescales (seconds, minutes, hours). The model was applied to determine changes in the penicillin pathway enzymes in time, calculate fluxes and analyze the flux control of the pathway. This led to a reassessment of the in vivo behavior of the pathway enzymes and in particular Acyl-CoA:Isopenicillin N Acyltransferase (AT). Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  20. 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...

  1. Penicillin skin testing is a safe and effective tool for evaluating penicillin allergy in the pediatric population.

    Science.gov (United States)

    Fox, Stephanie J; Park, Miguel A

    2014-01-01

    Penicillin skin testing has been validated in the evaluation of adult patients with penicillin allergy. However, the commercially available benzylpenicilloyl polylysine (Pre-Pen) is not indicated in the pediatric population. Moreover, the safety and validity of penicillin skin testing in the pediatric population has not been well studied. We describe the safety and validity of penicillin skin testing in the evaluation of children with a history of penicillin allergy. Children (penicillin allergy were evaluated with penicillin skin tests and were reviewed for basic demographics, penicillin skin test results, adverse drug reaction to penicillin after penicillin skin test, and adverse reaction to penicillin skin test. By using the χ(2) test, we compared the differences in the proportion of children and adults with a positive penicillin skin test. P value (penicillin skin testing; 703 of 778 patients had a negative penicillin skin test (90.4%), 66 had a positive test (8.5%), and 9 had an equivocal test (1.1%). Children were more likely to have a positive penicillin skin test (P penicillin skin test (52%) were challenged with penicillin, and 14 of 369 patients (3.8%) had an adverse drug reaction. No adverse reactions to penicillin skin testing were observed. Penicillin skin testing was safe and effective in the evaluation of children with a history of penicillin allergy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  3. 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.

  4. 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...

  5. 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.

  6. 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.)

  7. 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.

  8. Cephalosporin and penicillin cross-reactivity in patients allergic to penicillins.

    Science.gov (United States)

    Liu, X-D; Gao, N; Qiao, H-L

    2011-03-01

    Bata-lactam antibiotics are the most commonly used antibiotics which usually cause serious IgE-mediated allergic reactions. Of all bata-lactam antibiotics, penicillins have so far been the best-studied, but the studies of cephalosporins and their cross-reactivity with penicillins are rare. We sought to evaluate the IgE response in vitro and estimate cross-reactivity between penicillins and cephalosporins in patients allergic to penicillins. We studied 87 control subjects and 420 subjects allergic to penicillins. Radioallergosorbent test (RAST) was performed to detect eight types of specific-penicillin IgE and eleven types of specific-cephalosporin IgE. The cross-reactivity and different molecules recognition by IgE were studied with a radioallergosorbent inhibition test. Of 420 patients allergic to penicillins, 95 patients (22.62%) showed specific-cephalosporin IgE positive, 73 patients (17.38%) showed IgEs positive to both penicillins and cephalosporins. In specific-penicillin IgE positive group, the positive rate of specific-cephalosporin IgE was significantly higher than in specific-penicillin IgE negative group (27.14% vs. 14.57%, p penicillin-allergic patients we studied, and compared with patients who had negative amoxicillin-IgE, the positive rates of specific-ampicillin IgE and specific-cephalexin IgE were significantly higher in patients who had positive amoxicillin-IgE (14.43% vs. 3.72%, 14.00% vs. 2.96%, p penicillins; patients allergic to several penicillins are more likely to develop allergic reaction to cephalosporins; due to sensitization to the similar structural characteristics (nuclear and R1 side-chain), penicillin-allergic patients may develop cross-allergic reactions with not only first-generation but also third-generation cephalosporins.

  9. 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.

  10. 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/.

  11. 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...

  12. 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...

  13. 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.

  14. 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.

  15. Penicillin dust exposure and penicillin resistance among pharmaceutical workers in Tehran, Iran.

    Science.gov (United States)

    Farshad, Ali Asghar; Enferadi, Mojtaba; Bakand, Shahnaz; Jamshidi Orak, Rouhangiz; Mirkazemi, Roksana

    2016-07-01

    Antimicrobial resistance (AMR) adversely impacts the prevention and treatment of a wide range of infections and is considered as a serious threat to global public health. Occupational-related AMR is a neglected area of research. To assess exposure to penicillin dust, penicillin active materials, and to report the frequency of penicillin resistance among pharmaceutical workers in Tehran, Iran. A quasi-experimental study was conducted among workers on a penicillin production line in a pharmaceutical company (n = 60) and workers in a food producing company (n = 60). Data were collected via survey, air sampling, and throat swab. The mean overall concentrations of penicillin dust and penicillin active material were 6.6 and 4.3 mg/m 3 , respectively, in the pharmaceutical industry. Streptococcus pneumoniae (S. pneumoniae) was detected in 45% (27) individuals in the exposed group, 92.6% of which showed penicillin resistance. Resistance was significantly higher among workers in penicillin production line (p = 0.014). High level of AMR among workers in penicillin production line is a health risk for the workers as well as society as a whole through the spread of drug resistant micro-organisms.

  16. 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.

  17. 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.

  18. 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.

  19. One-week Oral Challenge with Penicillin in Diagnosis of Penicillin Allergy

    DEFF Research Database (Denmark)

    Hjortlund, Janni; Mørtz, Charlotte G; Skov, Per Stahl

    2012-01-01

    Many patients experience reactions during penicillin treatment. The diagnosis may be difficult and is mainly based on short-term tests. The European Network for Drug Allergy (ENDA) guidelines proposed for diagnosing penicillin allergy do not include long-term challenge. In this study a total of 405...... patients were evaluated. The ENDA guidelines were extended, to include a 7-day oral treatment (p.o.7) with penicillin for all patients who were negative in the ENDA programme. Among the 405 patients; 85 had an immediate reaction to penicillin, and a further 13 reacted during p.o.7. Among the 307 patients...... with a negative outcome, 88 had a case history of reaction to other β-lactam antibiotics and were subsequently tested with the culprit drug. Thirteen patients had a positive outcome: 3 on single-dose challenge and 10 during p.o.7. The extended penicillin diagnostic work-up was positive in 111 patients, 30...

  20. Effectiveness of penicillin, dicloxacillin and cefuroxime for penicillin-susceptible Staphylococcus aureus bacteraemia

    DEFF Research Database (Denmark)

    Nissen, Jette Lindbjerg; Skov, Robert; Knudsen, Inge Jenny Dahl

    2013-01-01

    OBJECTIVES: 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. METHODS: 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...... 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...

  1. 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....

  2. 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.

  3. An engineered yeast efficiently secreting penicillin.

    Directory of Open Access Journals (Sweden)

    Loknath Gidijala

    Full Text Available This study aimed at developing an alternative host for the production of penicillin (PEN. As yet, the industrial production of this beta-lactam antibiotic is confined to the filamentous fungus Penicillium chrysogenum. As such, the yeast Hansenula polymorpha, a recognized producer of pharmaceuticals, represents an attractive alternative. Introduction of the P. chrysogenum gene encoding the non-ribosomal peptide synthetase (NRPS delta-(L-alpha-aminoadipyl-L-cysteinyl-D-valine synthetase (ACVS in H. polymorpha, resulted in the production of active ACVS enzyme, when co-expressed with the Bacillus subtilis sfp gene encoding a phosphopantetheinyl transferase that activated ACVS. This represents the first example of the functional expression of a non-ribosomal peptide synthetase in yeast. Co-expression with the P. chrysogenum genes encoding the cytosolic enzyme isopenicillin N synthase as well as the two peroxisomal enzymes isopenicillin N acyl transferase (IAT and phenylacetyl CoA ligase (PCL resulted in production of biologically active PEN, which was efficiently secreted. The amount of secreted PEN was similar to that produced by the original P. chrysogenum NRRL1951 strain (approx. 1 mg/L. PEN production was decreased over two-fold in a yeast strain lacking peroxisomes, indicating that the peroxisomal localization of IAT and PCL is important for efficient PEN production. The breakthroughs of this work enable exploration of new yeast-based cell factories for the production of (novel beta-lactam antibiotics as well as other natural and semi-synthetic peptides (e.g. immunosuppressive and cytostatic agents, whose production involves NRPS's.

  4. 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...

  5. 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

  6. 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...

  7. 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

  8. 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.

  9. 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

  10. g+

    OpenAIRE

    Arenas, Gerardo

    2016-01-01

    La llamaré Nati Nul, para que tanto este nombre de fantasía como las iníciales del mismo mantengan en el anonimato el otro nombre de fantasía con quien alguien mantiene su anonimato para presentarse en una red social que conozco hace poco tiempo. Mi nuevo celular tenía un ícono desconocido (g+), la curiosidad me llevó a pulsarlo, y allí apareció la fotografía de Nati Nul, una mujer de más de cuarenta años, no favorecida por la naturaleza. En verdad, aparecieron seis selfies (que retrataban su...

  11. G

    OpenAIRE

    Wild, Nicole

    2014-01-01

    LA GIPSY Ballet-pantomime en trois actes et cinq tableaux d’Henri de Saint-Georges. Musique de François Benoist (A. I), Ambroise Thomas (A. II) et Aurelio Marliani (A. III). Création au Théâtre de l’Opéra (salle Le Peletier) le 28 janvier 1839 Chorégraphie de Joseph Mazilier. Décors de René Philastre et Charles Cambon. Costumes de Paul Lormier. A. I : Paysage d’Écosse. À g., le château de Lord Campbell. A. II, t. 1 : Vaste tente placée dans une rue d’Édimbourg. A. II, t. 2 : La grande foire ...

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 21 CFR 526.1696a - Penicillin G procaine.

    Science.gov (United States)

    2010-04-01

    ... treatment of mastitis caused by Streptococcus agalactiae, S. dysgalactiae, and S. uberus in lactating cows... of mastitis caused by Streptococcus agalactiae in dry cows. (3) Limitations. Discard all milk for 72... and 061623 in § 510.600(c) of this chapter. (d) Conditions of use in lactating cows—(1) Amount. Infuse...

  17. Biodegradation of penicillin-G wastewater using Phanerochate ...

    African Journals Online (AJOL)

    SERVER

    2007-06-18

    Jun 18, 2007 ... emission of toxic substances and formation of sludge. In recent years, a white rot fungus, ... sporium as a potential microorganism for the biodegrade- tion of polychlorinated ... 1990), paper mill bleach plant effluent (Fukui, 1992) and spentwash (Fahy et al., ..... Studies on biodegradation of toxic compounds.

  18. 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...

  19. 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

  20. 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.

  1. [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.

  2. Back to the Future: Penicillin-Susceptible Staphylococcus aureus.

    Science.gov (United States)

    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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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)

  9. 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...

  10. 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...

  11. 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

  12. 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.

  13. 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....

  14. 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.

  15. 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...

  16. 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.

  17. Nicolau syndrome following intramuscular benzathine penicillin

    Directory of Open Access Journals (Sweden)

    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.

  18. 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

  19. 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

  20. 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 ...

  1. 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

  2. What do I need to know about penicillin antibiotics?

    Science.gov (United States)

    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/.

  3. 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)

  4. 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.

  5. [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

  6. 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.

  7. [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.

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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...

  11. Penicillin-binding proteins in Actinobacteria.

    Science.gov (United States)

    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.

  12. 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.

  13. 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.

  14. A Proactive Approach to Penicillin Allergy Testing in Hospitalized Patients.

    Science.gov (United States)

    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.

  15. Documenting Penicillin Allergy: The Impact of Inconsistency

    Science.gov (United States)

    Shah, Nirav S.; Ridgway, Jessica P.; Pettit, Natasha; Fahrenbach, John; Robicsek, Ari

    2016-01-01

    Background Allergy documentation is frequently inconsistent and incomplete. The impact of this variability on subsequent treatment is not well described. Objective To determine how allergy documentation affects subsequent antibiotic choice. Design Retrospective, cohort study. Participants 232,616 adult patients seen by 199 primary care providers (PCPs) between January 1, 2009 and January 1, 2014 at an academic medical system. Main Measures Inter-physician variation in beta-lactam allergy documentation; antibiotic treatment following beta-lactam allergy documentation. Key Results 15.6% of patients had a reported beta-lactam allergy. Of those patients, 39.8% had a specific allergen identified and 22.7% had allergic reaction characteristics documented. Variation between PCPs was greater than would be expected by chance (all ppenicillins”) (24.0% to 58.2%) and documentation of the reaction characteristics (5.4% to 51.9%). After beta-lactam allergy documentation, patients were less likely to receive penicillins (Relative Risk [RR] 0.16 [95% Confidence Interval: 0.15–0.17]) and cephalosporins (RR 0.28 [95% CI 0.27–0.30]) and more likely to receive fluoroquinolones (RR 1.5 [95% CI 1.5–1.6]), clindamycin (RR 3.8 [95% CI 3.6–4.0]) and vancomycin (RR 5.0 [95% CI 4.3–5.8]). Among patients with beta-lactam allergy, rechallenge was more likely when a specific allergen was identified (RR 1.6 [95% CI 1.5–1.8]) and when reaction characteristics were documented (RR 2.0 [95% CI 1.8–2.2]). Conclusions Provider documentation of beta-lactam allergy is highly variable, and details of the allergy are infrequently documented. Classification of a patient as beta-lactam allergic and incomplete documentation regarding the details of the allergy lead to beta-lactam avoidance and use of other antimicrobial agents, behaviors that may adversely impact care quality and cost. PMID:26981866

  16. 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

  17. 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

  18. 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...

  19. 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...

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. 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...

  8. 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

  9. 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.

  10. 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)

  11. 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.

  12. Evaluation of Penicillin Allergy in the Hospitalized Patient: Opportunities for Antimicrobial Stewardship.

    Science.gov (United States)

    Chen, Justin R; Khan, David A

    2017-06-01

    Penicillin allergy is often misdiagnosed and is associated with adverse consequences, but testing is infrequently done in the hospital setting. This article reviews historical and contemporary innovations in inpatient penicillin allergy testing and its impact on antimicrobial stewardship. Adoption of the electronic medical record allows rapid identification of admitted patients carrying a penicillin allergy diagnosis. Collaboration with clinical pharmacists and the development of computerized clinical guidelines facilitates increased testing and appropriate use of penicillin and related β-lactams. Education of patients and their outpatient providers is the key to retaining the benefits of penicillin allergy de-labeling. Penicillin allergy testing is feasible in the hospital and offers tangible benefits towards antimicrobial stewardship. Allergists should take the lead in this endeavor and work towards overcoming personnel limitations by partnering with other health care providers and incorporating technology that improves the efficiency of allergy evaluation.

  13. 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.

  14. 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 ...

  15. 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.

  16. 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.

  17. 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...

  18. 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....

  19. 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.

  20. 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.

  1. 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)

  2. 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.

  3. 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.

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

    Science.gov (United States)

    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.

  5. 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.

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

    Science.gov (United States)

    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.

  7. 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.

  8. 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.

  9. 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.

  10. 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....

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

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

    Science.gov (United States)

    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.

  17. 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

  18. 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 0.87μg

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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 ...

  4. Relationship between focal penicillin spikes and cortical spindles in the cerveau isolé cat.

    Science.gov (United States)

    McLachlan, R S; Kaibara, M; Girvin, J P

    1983-01-01

    Using the unanesthetized, cerveau isolé preparation in the cat, the association between artificially induced penicillin (PCN) spikes and spontaneously occurring electrocorticographic (ECoG) spindles was investigated. Spikes were elicited by surface application of small pledgets of PCN. After the application of PCN, there was a decrease in spindle amplitude but no change in frequency, duration, or spindle wave frequency in the area of the focus. Examination of the times of occurrence of the spikes and spindles disclosed that in the majority of cases, within a few minutes of the initiation of the foci, there was very high simultaneity, usually 100% between the occurrences of these two events. Examination of the times of occurrence of the spikes within the ECoG spindles failed to disclose any compelling evidence which would favor either the hypothesis that spikes "trigger" spindles or the hypothesis that spindles predispose to focal spikes. Thus, whether spikes trigger spindles, or spikes simply occur in a nonspecific manner during the occurrence of the spindle, or whether it is a combination of both these explanations, must remain an open question on the basis of the data available.

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

    African Journals Online (AJOL)

    The aim of this study is to screen for PGA producing Escherichia coli isolates as well as the cloning and recombinant expression of PGA for high level enzyme production. Bacteria isolated from environmental and clinical samples were identified by standard microbiological tests and then E. coli isolates were subjected to

  6. Potential of Pichia pastoris for the production of industrial penicillin G acylase

    Czech Academy of Sciences Publication Activity Database

    Marešová, Helena; Palyzová, Andrea; Plačková, Martina; Grulich, Michal; Rajasekar, V.W.; Štěpánek, Václav; Kyslíková, Eva; Kyslík, Pavel

    2017-01-01

    Roč. 62, č. 5 (2017), s. 417-424 ISSN 0015-5632 Institutional support: RVO:61388971 Keywords : HETEROLOGOUS PROTEIN-PRODUCTION * ESCHERICHIA-COLI * BACILLUS-MEGATERIUM Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 1.521, year: 2016

  7. 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.

  8. 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...

  9. 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 ...

  10. 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...

  11. 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...

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Analysis of multidrug resistant group B streptococci with reduced penicillin susceptibility forming small, less hemolytic colonies.

    Directory of Open Access Journals (Sweden)

    Hirotsugu Banno

    Full Text Available Group B streptococci (GBS; Streptococcus agalactiae are the leading cause of neonatal invasive diseases and are also important pathogens for elderly adults. Until now, nearly all GBS with reduced penicillin susceptibility (PRGBS have shown β-hemolytic activity and grow on sheep blood agar. However, we have previously reported three PRGBS clinical isolates harboring a CylK deletion that form small less hemolytic colonies. In this study, we examined the causes of small, less hemolytic colony formation in these clinical isolates. Isogenic strains were sequenced to identify the mutation related to a small colony size. We identified a 276_277insG nucleic acid insertion in the thiamin pyrophosphokinase (tpk gene, resulting in premature termination at amino acid 103 in TPK, as a candidate mutation responsible for small colony formation. The recombinant strain Δtpk, which harbored the 276_277insG insertion in the tpk gene, showed small colony formation. The recombinant strain ΔcylK, which harbored the G379T substitution in cylK, showed a reduction in hemolytic activity. The phenotypes of both recombinant strains were complemented by the expression of intact TPK or CylK, respectively. Moreover, the use of Rapid ID 32 API and VITEK MS to identify strains as GBS was evaluated clinical isolates and recombinant strains. VITEK MS, but not Rapid ID 32 API, was able to accurately identify the strains as GBS. In conclusion, we determined that mutations in tpk and cylK caused small colonies and reduced hemolytic activity, respectively, and characterized the clinical isolates in detail.

  9. 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...

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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)

  15. Solid phase extraction of penicillins from milk by using sacrificial silica beads as a support for a molecular imprint

    International Nuclear Information System (INIS)

    Giovannoli, Cristina; Anfossi, Laura; Biagioli, Flavia; Passini, Cinzia; Baggiani, Claudio

    2013-01-01

    We have prepared molecularly imprinted beads with molecular recognition capability for target molecules containing the penicillanic acid substructure. They were prepared by (a) grafting mesoporous silica beads with 6-aminopenicillanic acid as the mimic template, (b) filling the pores with a polymerized mixture of methacrylic acid and trimethylolpropane trimethacrylate, and (c) removing the silica support with ammonium fluoride. The resulting imprinted beads showed good molecular recognition capability for various penicillanic species, while antibiotics such as cephalosporins or chloramphenicol were poorly recognized. The imprinted beads were used to extract penicillin V, nafcillin, oxacillin, cloxacillin and dicloxacillin from skimmed and deproteinized milk in the concentration range of 5–100 μg·L −1 . The extracts were then analyzed by micellar electrokinetic chromatography by applying reverse polarity staking as an in-capillary preconcentration step, and this resulted in a fast and affordable method within the MRL levels, characterized by minimal pretreatment steps and recoveries of 64–90 %. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. 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

  19. 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

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.)

  7. 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...

  8. 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.

  9. 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.

  10. PcFKH1, a novel regulatory factor from the forkhead family, controls the biosynthesis of penicillin in Penicillium chrysogenum.

    Science.gov (United States)

    Domínguez-Santos, Rebeca; García-Estrada, Carlos; Kosalková, Katarina; Prieto, Carlos; Santamarta, Irene; Martín, Juan-Francisco

    2015-08-01

    Penicillin biosynthesis in Penicillium chrysogenum (re-identified as Penicillium rubens) is a good example of a biological process subjected to complex global regulatory networks and serves as a model to study fungal secondary metabolism. The winged-helix family of transcription factors recently described, which includes the forkhead type of proteins, is a key type of regulatory proteins involved in this process. In yeasts and humans, forkhead transcription factors are involved in different processes (cell cycle regulation, cell death control, pre-mRNA processing and morphogenesis); one member of this family of proteins has been identified in the P. chrysogenum genome (Pc18g00430). In this work, we have characterized this novel transcription factor (named PcFKH1) by generating knock-down mutants and overexpression strains. Results clearly indicate that PcFKH1 positively controls antibiotic biosynthesis through the specific interaction with the promoter region of the penDE gene, thus regulating penDE mRNA levels. PcFKH1 also binds to the pcbC promoter, but with low affinity. In addition, it also controls other ancillary genes of the penicillin biosynthetic process, such as phlA (encoding phenylacetyl CoA ligase) and ppt (encoding phosphopantetheinyl transferase). PcFKH1 also plays a role in conidiation and spore pigmentation, but it does not seem to be involved in hyphal morphology or cell division in the improved laboratory reference strain Wisconsin 54-1255. A genome-wide analysis of processes putatively coregulated by PcFKH1 and PcRFX1 (another winged-helix transcription factor) in P. chrysogenum provided evidence of the global effect of these transcription factors in P. chrysogenum metabolism. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Characterization of Extracellular Penicilin G Acylase Produced by A New Local Strain of Bacillus subtilis BAC4

    Directory of Open Access Journals (Sweden)

    SUPARTONO

    2008-06-01

    Full Text Available Penicillin G acylase (PGA which catalyses penicillin G hydrolysis reaction is a key enzyme for the industrial production of penicilin G derivatives used in therapeutics. A new local strain of Bacillus subtilis BAC4 was found capable of producing extracellular PGA. However, characteristics of this extracellular PGA are not known. The goal of this research was to characterize the extracellular PGA produced by B. subtilis BAC4. Enzyme production was carried out by batch fermentation, followed by enzyme purification and characterization of the PGA. The PGA activity was determined by the Kornfeld method, with optimal activity for hydrolysing penicillin G observed at 43 °C and pH 8.5. The activation energy of penicillin G hydrolysis by the PGA of B. subtilis BAC4 was determined as 4.9 kcal.mol−1 and Vmax and Km values were found to be 0.7 μmole.min−1.mg−1 and 3.5 mM respectively. PGA catalytic activity was competitively inhibited by phenylacetic acid with an inhibition constant, Ki(PAA, of 347.2 mM. It was concluded that the extracellular PGA of B. subtilis BAC4 can hydrolyse penicillin G efficiently.

  17. Characterization of Extracellular Penicilin G Acylase Produced by A New Local Strain of Bacillus subtilis BAC4

    Directory of Open Access Journals (Sweden)

    SUPARTONO

    2008-06-01

    Full Text Available Penicillin G acylase (PGA which catalyses penicillin G hydrolysis reaction is a key enzyme for the industrial production of penicilin G derivatives used in therapeutics. A new local strain of Bacillus subtilis BAC4 was found capable of producing extracellular PGA. However, characteristics of this extracellular PGA are not known. The goal of this research was to characterize the extracellular PGA produced by B. subtilis BAC4. Enzyme production was carried out by batch fermentation, followed by enzyme purification and characterization of the PGA. The PGA activity was determined by the Kornfeld method, with optimal activity for hydrolysing penicillin G observed at 43 oC and pH 8.5. The activation energy of penicillin G hydrolysis by the PGA of B. subtilis BAC4 was determined as 4.9 kcal.mol-1 and Vmax and Km values were found to be 0.7 µmole.min-1.mg-1 and 3.5 mM respectively. PGA catalytic activity was competitively inhibited by phenylacetic acid with an inhibition constant, Ki(PAA, of 347.2 mM. It was concluded that the extracellular PGA of B. subtilis BAC4 can hydrolyse penicillin G efficiently.

  18. 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...

  19. 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

  20. 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)

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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...

  10. The experience of intramuscular benzathine penicillin for prophylaxis of recurrent cellulitis: A cohort study

    Directory of Open Access Journals (Sweden)

    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.

  11. 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)

  12. 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.

  13. Temporal relationships exist between cecum, ileum and litter bacterial microbiomes in a commercial turkey flock, and subtherapeutic penicillin treatment impacts ileum bacterial community establishment

    Directory of Open Access Journals (Sweden)

    Jessica L Danzeisen

    2015-11-01

    Full Text Available Gut health is paramount for commercial poultry production, and improved methods to assess gut health are critically needed to better understand how the avian gastrointestinal tract matures over time. One important aspect of gut health is the totality of bacterial populations inhabiting different sites of the avian gastrointestinal tract, and associations of these populations with the poultry farm environment, since these bacteria are thought to drive metabolism and prime the developing host immune system. In this study, a single flock of commercial turkeys was followed over the course of twelve weeks to examine bacterial microbiome inhabiting the ceca, ileum, and corresponding poultry litter. Furthermore, the effects of low-dose, growth-promoting penicillin treatment (50 g/ton in feed on the ileum bacterial microbiome were also examined during the early brood period. The cecum and ileum bacterial communities of turkeys were distinct, yet shifted in parallel to one another over time during bird maturation. Corresponding poultry litter was also distinct yet more closely represented the ileal bacterial populations than cecal bacterial populations, and also changed parallel to ileum bacterial populations over time. Penicillin applied at low dose in feed significantly enhanced early weight gain in commercial poults, and this correlated with predictable shifts in the ileum bacterial populations in control versus treatment groups. Overall, this study identified the dynamics of the turkey gastrointestinal microbiome during development, correlations between bacterial populations in the gastrointestinal tract and the litter environment, and the impact of low-dose penicillin on modulation of bacterial communities in the ileum. Such modulations provide a target for alternatives to low-dose antibiotics.

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. G5..., G6..., G7..., G8..., G?

    OpenAIRE

    Monteiro, António

    2001-01-01

    O G8 tem as suas raízes no primitivo embrião do G5 quando, em 1973, o então Secretário de Estado do Tesouro americano, George Schultz, convocou os Ministros das Finanças da França, Japão, Reino Unido e República Federal da Alemanha para uma reunião. O objectivo era analisar como fazer face à primeira crise do petróleo da OPEC e subsequente recessão económica nos países mais industrializados, ao colapso do sistema monetário das taxas de câmbio de paridades fixas de Bretton-Woods e ao alargamen...

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. 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)

  9. 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

  10. 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.

  11. Casein phosphopeptides and CaCl2 increase penicillin production and cause an increment in microbody/peroxisome proteins in Penicillium chrysogenum.

    Science.gov (United States)

    Domínguez-Santos, Rebeca; Kosalková, Katarina; García-Estrada, Carlos; Barreiro, Carlos; Ibáñez, Ana; Morales, Alejandro; Martín, Juan-Francisco

    2017-03-06

    Transport of penicillin intermediates and penicillin secretion are still poorly characterized in Penicillium chrysogenum (re-identified as Penicillium rubens). Calcium (Ca 2+ ) plays an important role in the metabolism of filamentous fungi, and casein phosphopeptides (CPP) are involved in Ca 2+ internalization. In this study we observe that the effect of CaCl 2 and CPP is additive and promotes an increase in penicillin production of up to 10-12 fold. Combination of CaCl 2 and CPP greatly promotes expression of the three penicillin biosynthetic genes. Comparative proteomic analysis by 2D-DIGE, identified 39 proteins differentially represented in P. chrysogenum Wisconsin 54-1255 after CPP/CaCl 2 addition. The most interesting group of overrepresented proteins were a peroxisomal catalase, three proteins of the methylcitrate cycle, two aminotransferases and cystationine β-synthase, which are directly or indirectly related to the formation of penicillin amino acid precursors. Importantly, two of the enzymes of the penicillin pathway (isopenicillin N synthase and isopenicillin N acyltransferase) are clearly induced after CPP/CaCl 2 addition. Most of these overrepresented proteins are either authentic peroxisomal proteins or microbody-associated proteins. This evidence suggests that addition of CPP/CaCl 2 promotes the formation of penicillin precursors and the penicillin biosynthetic enzymes in peroxisomes and vesicles, which may be involved in transport and secretion of penicillin. Penicillin biosynthesis in Penicillium chrysogenum is one of the best characterized secondary metabolism processes. However, the mechanism by which penicillin is secreted still remains to be elucidated. Taking into account the role played by Ca 2+ and CPP in the secretory pathway and considering the positive effect that Ca 2+ exerts on penicillin production, the analysis of global protein changes produced after CPP/CaCl 2 addition is very helpful to decipher the processes related to the

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

    Science.gov (United States)

    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

  18. 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...

  19. 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...

  20. 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.

  1. Pharmacodynamic Analysis and Clinical Trial of Amoxicillin Sprinkle Administered Once Daily for 7 Days Compared to Penicillin V Potassium Administered Four Times Daily for 10 Days in the Treatment of Tonsillopharyngitis Due to Streptococcus pyogenes in Children▿

    Science.gov (United States)

    Pichichero, M. E.; Casey, J. R.; Block, S. L.; Guttendorf, R.; Flanner, H.; Markowitz, D.; Clausen, S.

    2008-01-01

    An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC90 of 0.06 μg/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, −12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of ≥85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, −11.6% to −0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily T >MIC90 more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between longer

  2. 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.

  3. Determination of penicillin-G procaine in kidney, muscle, serum, and urine of heavy sows after intramuscular administration

    Science.gov (United States)

    The United States Department of Agriculture Food Safety and Inspection Service (FSIS) recently adapted the use of the Charm Kidney Inhibition Swab (KIS) test for screening antibiotics on-site, along with a LC-MS/MS method for confirmation of KIS-positive samples. A study with 126 heavy sows (227.0 ...

  4. OPTICAL STUDIES OF PENICILLIN GROUP IN RELATION TO THEIR MEDICAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    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.

  5. 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....../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...

  6. 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...

  7. In vitro susceptibility of bovine mastitis pathogens to a combination of penicillin and framycetin: development of interpretive criteria for testing by broth microdilution and disk diffusion.

    Science.gov (United States)

    Pillar, C M; Stoneburner, A; Shinabarger, D L; Abbeloos, E; Goby, L; Bradley, Andrew J

    2014-10-01

    Dry cow therapy is an important part of mastitis control. This therapy typically consists of an antibiotic or antibiotics administered at a single dose by intramammary infusion at dry off to treat or prevent infection by prevalent mastitis pathogens. A combination dry cow therapy consisting of the active components penicillin and framycetin is currently used in several countries. Despite its use, standardized methods for the susceptibility testing of this combination against mastitis pathogens have not been established. In this study, which used Clinical and Laboratory Standards Institute methodology, preliminary interpretive criteria for the broth microdilution minimum inhibitory concentration (MIC) testing of mastitis pathogens to penicillin combined with framycetin (2:1 wt/wt) were established based on the amount of drug achieved and maintained postadministration in the udder. Based on resulting MIC distributions of recent veterinary field isolates and a subset of isolates preselected for resistance to β-lactams or aminoglycosides and concentrations achieved postadministration, criteria for broth microdilution testing of the combination (susceptible, intermediate, resistant in micrograms per milliliter) were set as follows: Escherichia coli ≤8/4, 16/8, ≥32/16; Staphylococcus spp. ≤2/1, 4/2-8/4, >16/8; Streptococcus uberis and Streptococcus dysgalactiae 4/2. A disk diffusion test using disks containing 100 μg of framycetin and 10 IU of penicillin was also developed, and preliminary interpretive criteria (susceptible, intermediate, resistant in millimeters) were set based on correlation to broth MIC values and the minimization of interpretive errors between isolates tested concurrently by broth microdilution and disk diffusion as follows: E. coli ≥18, 16-17, ≤15; Staphylococcus spp. ≥21, 18-20, ≤17; Strep. uberis and Strep. dysgalactiae ≥21, 19-20, ≤18. In addition, ranges for the quality control of the testing of this combination by both broth

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. [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.

  17. Subfamily-specific adaptations in the structures of two penicillin-binding proteins from Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  19. 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.

  20. Comparative effectiveness of injectable penicillin versus a combination of penicillin and gentamicin in children with pneumonia characterised by indrawing in Kenya: protocol for an observational study.

    Science.gov (United States)

    Malla, Lucas; Perera-Salazar, Rafael; McFadden, Emily; English, Mike

    2017-09-18

    WHO treatment guidelines are widely recommended for guiding treatment for millions of children with pneumonia every year across multiple low-income and middle-income countries. Guidelines are based on synthesis of available evidence that provides moderate certainty in evidence of effects for forms of pneumonia that can result in hospitalisation. However, trials have included fewer children from Africa than other settings, and it is suggested that African children with pneumonia have higher mortality. Thus, despite improving access to recommended treatments and deployment with high coverage of childhood vaccines, pneumonia remains one of the top causes of mortality for children in Kenya. Establishing whether there are benefits of alternative treatment regimens to help reduce mortality would require pragmatic clinical trials. However, these remain relatively expensive and time consuming. This protocol describes an approach to using secondary analysis of a new, large observational dataset as a potentially cheaper and quicker way to examine the comparative effectiveness of penicillin versus penicillin plus gentamicin in treatment of indrawing pneumonia. Addressing this question is important, as although it is now recommended that this form of pneumonia is treated with oral medication as an outpatient, it remains associated with non-trivial mortality that may be higher outside trial populations. We will use a large observational dataset that captures data on all admissions to 13 Kenyan county hospitals. These data represent the findings of clinicians in practice and, because the system was developed for large observational research, pose challenges of non-random treatment allocation and missing data. To overcome these challenges, this analysis will use a rigorous approach to study design, propensity score methods and multiple imputation to minimise bias. The primary data are held by hospitals participating in the Kenyan Clinical Information Network project with de

  1. 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.

  2. Block of GABA(A) receptor ion channel by penicillin: electrophysiological and modeling insights toward the mechanism.

    Science.gov (United States)

    Rossokhin, Alexey V; Sharonova, Irina N; Bukanova, Julia V; Kolbaev, Sergey N; Skrebitsky, Vladimir G

    2014-11-01

    GABA(A) receptors (GABA(A)R) mainly mediate fast inhibitory neurotransmission in the central nervous system. Different classes of modulators target GABA(A)R properties. Penicillin G (PNG) belongs to the class of noncompetitive antagonists blocking the open GABA(A)R and is a prototype of β-lactam antibiotics. In this study, we combined electrophysiological and modeling approaches to investigate the peculiarities of PNG blockade of GABA-activated currents recorded from isolated rat Purkinje cells and to predict the PNG binding site. Whole-cell patch-сlamp recording and fast application system was used in the electrophysiological experiments. PNG block developed after channel activation and increased with membrane depolarization suggesting that the ligand binds within the open channel pore. PNG blocked stationary component of GABA-activated currents in a concentration-dependent manner with IC50 value of 1.12mM at -70mV. The termination of GABA and PNG co-application was followed by a transient tail current. Protection of the tail current from bicuculline block and dependence of its kinetic parameters on agonist affinity suggest that PNG acts as a sequential open channel blocker that prevents agonist dissociation while the channel remains blocked. We built the GABA(A)R models based on nAChR and GLIC structures and performed an unbiased systematic search of the PNG binding site. Monte-Carlo energy minimization was used to find the lowest energy binding modes. We have shown that PNG binds close to the intracellular vestibule. In both models the maximum contribution to the energy of ligand-receptor interactions revealed residues located on the level of 2', 6' and 9' rings formed by a bundle of M2 transmembrane segments, indicating that these residues most likely participate in PNG binding. The predicted structural models support the described mechanism of PNG block. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

    Science.gov (United States)

    Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

    2017-03-15

    Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  4. 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.

  5. 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.

  6. Penicillin kills Chlamydia following the fusion of bacteria with lysosomes and prevents genital inflammatory lesions in C. muridarum-infected mice.

    Directory of Open Access Journals (Sweden)

    Maud Dumoux

    Full Text Available The obligate intracellular bacterium Chlamydia exists as two distinct forms. Elementary bodies (EBs are infectious and extra-cellular, whereas reticulate bodies (RBs replicate within a specialized intracellular compartment termed an 'inclusion'. Alternative persistent intra-cellular forms can be induced in culture by diverse stimuli such as IFNγ or adenosine/EHNA. They do not grow or divide but revive upon withdrawal of the stimulus and are implicated in several widespread human diseases through ill-defined in vivo mechanisms. β-Lactam antibiotics have also been claimed to induce persistence in vitro. The present report shows that upon penicillin G (pG treatment, inclusions grow as fast as those in infected control cells. After removal of pG, Chlamydia do not revert to RBs. These effects are independent of host cell type, serovar, biovar and species of Chlamydia. Time-course experiments demonstrated that only RBs were susceptible to pG. pG-treated bacteria lost their control over host cell apoptotic pathways and no longer expressed pre-16S rRNA, in contrast to persistent bacteria induced with adenosine/EHNA. Confocal and live-video microscopy showed that bacteria within the inclusion fused with lysosomal compartments in pG-treated cells. That leads to recruitment of cathepsin D as early as 3 h post pG treatment, an event preceding bacterial death by several hours. These data demonstrate that pG treatment of cultured cells infected with Chlamydia results in the degradation of the bacteria. In addition we show that pG is significantly more efficient than doxycycline at preventing genital inflammatory lesions in C. muridarum-C57Bl/6 infected mice. These in vivo results support the physiological relevance of our findings and their potential therapeutic applications.

  7. IgE to penicillins with different specificities can be identified by a multiepitope macromolecule: Bihaptenic penicillin structures and IgE specificities.

    Science.gov (United States)

    Ariza, A; Barrionuevo, E; Mayorga, C; Montañez, M I; Perez-Inestrosa, E; Ruiz-Sánchez, A; Rodríguez-Guéant, R M; Fernández, T D; Guéant, J L; Torres, M J; Blanca, M

    2014-04-01

    Quantitation of specific IgE by immunoassay is a recommended in vitro test for the diagnosis of immediate hypersensitivity reactions to betalactams (BLs), particularly when skin test results are negative. IgE antibodies that recognize the common nuclear structure of all BLs or the specific side chain structure can be mainly distinguished by immunoassays. The aim of this study was to develop an immunoassay system to detect IgE antibodies with different specificities. Cellulose discs conjugated with benzylpenicillin (BP), amoxicillin (AX) or both drugs, with poly-l-lysine (PLL) as carrier molecule, were used as solid phases in the radioallergosorbent test (RAST). Direct and inhibition radioimmunoassay studies were made to verify the structures recognized by serum IgE antibodies from penicillin-allergic patients. Our results indicated that the addition of both haptens did not decrease the capacity to capture IgE when serum specific to either BP or AX was used, at least in terms of sensitivity. In addition, the inclusion of two haptens improved significantly the levels of IgE detection in patients who recognized both BP and AX. Therefore, the use of a solid phase with a carrier molecule conjugated with two determinants (AX and BP) is helpful to recognize IgE antibodies against either of these determinants and is useful for screening sera with different specificities. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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...

  14. 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

  15. 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

  16. G Marimuthu

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. G Marimuthu. Articles written in Resonance – Journal of Science Education. Volume 1 Issue 3 March 1996 pp 103-110 Feature Article. Nature Watch Diversity of Bats · G Marimuthu · More Details Fulltext PDF. Volume 1 Issue 5 May 1996 pp 40-48 General Article.

  17. G Parthasarathy

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. G Parthasarathy. Articles written in Bulletin of Materials Science. Volume 30 Issue 1 February 2007 pp 19-21 Nanomaterials. A novel method for synthesizing nano-crystalline MgTiO3 geikielite · G Parthasarathy S V Manorama · More Details Abstract Fulltext PDF. We report ...

  18. G Padmanaban

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. G Padmanaban. Articles written in Resonance – Journal of Science Education. Volume 21 Issue 4 April 2016 pp 327-338 General Article. Nobel for Artemisinin: Curcumin is Waiting for Ages · G Padmanaban · More Details Abstract Fulltext PDF ...

  19. G Prathap

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. G Prathap. Articles written in Resonance – Journal of Science Education. Volume 1 Issue 11 November 1996 pp 2-3 Article-in-a-Box. Karl Popper · G Prathap · More Details Fulltext PDF ...

  20. G Ambika

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. G Ambika. Articles written in Resonance – Journal of Science Education. Volume 20 Issue 3 March 2015 pp 198-205 General Article. Ed Lorenz: Father of the 'Butterfly Effect' · G Ambika · More Details Fulltext PDF ...

  1. 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.

  2. Biochemical characterization of the 49 kDa penicillin-binding protein of Mycobacterium smegmatis.

    Science.gov (United States)

    Mukherjee, T; Basu, D; Mahapatra, S; Goffin, C; van Beeumen, J; Basu, J

    1996-01-01

    The 49 kDa penicillin-binding protein (PBP) of Mycobacterium smegmatis catalyses the hydrolysis of the peptide or S-ester bond of carbonyl donors R1-CONH-CHR2-COX-CHR2-COO- (where X is NH or S). In the presence of a suitable amino acceptor, the reaction partitions between the transpeptidation and hydrolysis pathways, with the amino acceptor, behaving as a simple alternative nucleophile at the level of the acyl-enzyme. By virtue of its N-terminal sequence similarity, the 49 kDa PBP represents one of the class of monofunctional low-molecular-mass PBPs. An immunologically related protein of M(r) 52,000 is present in M. tuberculosis. The 49 kDa PBP is sensitive towards amoxycillin, imipenem, flomoxef and cefoxitin. PMID:8947487

  3. From penicillin-streptomycin to amikacin-vancomycin: antibiotic decontamination of cardiovascular homografts in Singapore.

    Directory of Open Access Journals (Sweden)

    Wee Ling Heng

    Full Text Available BACKGROUND: In February 2012, the National Cardiovascular Homograft Bank (NCHB became the first tissue bank outside of North America to receive accreditation from the American Association of Tissue Banks. From 2008 to 2009, NCHB had been decontaminating its cardiovascular homografts with penicillin and streptomycin. The antibiotic decontamination protocol was changed in January 2010 as amikacin and vancomycin were recommended, in order to cover bacteria isolated from post-recovery and post- antibiotic incubation tissue cultures. AIM: The objective of this study is to determine the optimal incubation conditions for decontamination of homografts by evaluating the potencies of amikacin and vancomycin in different incubation conditions. Retrospective reviews of microbiological results were also performed for homografts recovered from 2008 to 2012, to compare the effectiveness of penicillin-streptomycin versus the amikacin-vancomycin regimens. METHODS: Based on microbiological assays stated in United States Pharmacopeia 31, potency of amikacin was evaluated by turbidimetric assay using Staphylococcus aureus, while vancomycin was by diffusion assay using Bacillus subtilis sporulate. Experiments were performed to investigate the potencies of individual antibiotic 6-hours post incubation at 4°C and 37°C and 4°C for 24 hours, after the results suggested that amikacin was more potent at lower temperature. FINDINGS: Tissue incubation at 4°C for 24 hours is optimal for both antibiotics, especially for amikacin, as its potency falls drastically at 37°C. CONCLUSION: The decontamination regimen of amikacin-vancomycin at 4°C for 24 hours is effective. Nevertheless, it is imperative to monitor microbiological trends closely and evaluate the efficacy of current antibiotics regimen against emerging strains of micro-organisms.

  4. 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

  5. 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

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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...

  12. 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

  13. 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)

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

    OpenAIRE

    Pehlivanoglu, Filiz; Sengoz, Gonul; Şengöz, Gönül; Gursoy, Sevtap

    2015-01-01

    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 penicilli...

  15. 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

  16. 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

    2013-01-01

    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

  17. 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.

  18. ZnO Nanorods Based Enzymatic Biosensor for Selective Determination of Penicillin

    Directory of Open Access Journals (Sweden)

    Magnus Willander

    2011-10-01

    Full Text Available In this study, we have successfully demonstrated the fabrication of a biosensor based on well aligned single-crystal zinc oxide (ZnO nanorods which were grown on gold coated glass substrate using a low temperature aqueous chemical growth (ACG method. The ZnO nanorods were immobilized with penicillinase enzyme using the physical adsorption approach in combination with N-5-azido-2-nitrobenzoyloxysuccinimide (ANB-NOS as cross linking molecules. The potentiometric response of the sensor configuration revealed good linearity over a large logarithmic concentration range from 100 µM to 100 mM. During the investigations, the proposed sensor showed a good stability with high sensitivity of ~121 mV/decade for sensing of penicillin. A quick electrochemical response of less than 5 s with a good selectivity, repeatability, reproducibility and a negligible response to common interferents such as Na1+, K1+, d-glucose, l-glucose, ascorbic acid, uric acid, urea, sucrose, lactose, glycine, penicilloic acid and cephalosporins, was observed.

  19. ZnO Nanorods Based Enzymatic Biosensor for Selective Determination of Penicillin.

    Science.gov (United States)

    Ibupoto, Zafar Hussain; Ali, Syed Muhammad Usman; Khun, Kimleang; Chey, Chan Oeurn; Nur, Omer; Willander, Magnus

    2011-10-27

    In this study, we have successfully demonstrated the fabrication of a biosensor based on well aligned single-crystal zinc oxide (ZnO) nanorods which were grown on gold coated glass substrate using a low temperature aqueous chemical growth (ACG) method. The ZnO nanorods were immobilized with penicillinase enzyme using the physical adsorption approach in combination with N-5-azido-2-nitrobenzoyloxysuccinimide (ANB-NOS) as cross linking molecules. The potentiometric response of the sensor configuration revealed good linearity over a large logarithmic concentration range from 100 µM to 100 mM. During the investigations, the proposed sensor showed a good stability with high sensitivity of ~121 mV/decade for sensing of penicillin. A quick electrochemical response of less than 5 s with a good selectivity, repeatability, reproducibility and a negligible response to common interferents such as Na1+, K1+, d-glucose, l-glucose, ascorbic acid, uric acid, urea, sucrose, lactose, glycine, penicilloic acid and cephalosporins, was observed.

  20. Therapeutic Efficacy of Meropenem for Treatment of Experimental Penicillin-Resistant Pneumococcal Meningitis

    Science.gov (United States)

    Kim, Shin-Woo; Jin, Joung Hwa; Kang, Soo Jung; Jung, Sook-In; Kim, Yeon-Sook; Kim, Choon-Kwan; Lee, Hyuck; Oh, Won Sup; Kim, Sungmin; Peck, Kyong Ran

    2004-01-01

    With the widespread emergence of antimicrobial resistance, combination regimens of ceftriaxone and vancomycin (C+V) or ceftriaxone and rifampin (C+R) are recommended for empirical treatment of pneumococcal meningitis. To evaluate the therapeutic efficacy of meropenem (M), we compared various treatment regimens in arabbit model of meningitis caused by penicillin-resistant Streptococcus pneumoniae (PRSP). Therapeutic efficacy was also evaluated by the final bacterial concentration in the cerebrospinal fluid (CSF) at 24 hr. Each group consisted of six rabbits. C+V cleared the CSF at 10 hr, but regrowth was noted in 3 rabbits at 24 hr. Meropenem monotherapy resulted in sterilization at 10 hr, but regrowth was observed in all 6 rabbits at 24 hr. M+V also resulted in sterilization at 10 hr, but regrowth was observed in 2 rabbits at 24 hr. M+V was superior to the meropenem monotherapy at 24 hr (reduction of 4.8 vs. 1.8 log10 cfu/mL, respectively; p=0.003). The therapeutic efficacy of M+V was comparable to that of C+V (reduction of 4.8 vs. 4.0 log10 cfu/mL, respectively; p=0.054). The meropenem monotherapy may not be a suitable choice for PRSP meningitis, while combination of meropenem and vancomycin could be a possible alternative in the treatment of PRSP meningitis. PMID:14966336

  1. Antibacterial Derivatives of Ciprofloxacin to Inhibit Growth of Necrotizing Fasciitis Associated Penicillin Resistant Escherichia coli

    Directory of Open Access Journals (Sweden)

    Ronald Bartzatt

    2013-01-01

    Full Text Available Escherichia coli (E. coli is associated with necrotizing fasciitis (type I and can induce enough damage to tissue causing hypoxia. Three ester derivatives of the broad-spectrum antibiotic ciprofloxacin were placed into bacteria culture simultaneously with the parent ciprofloxacin (drug 1 to ascertain the level of antibacterial activity. The n-propyl (drug 2, n-pentyl (drug 3, and n-octyl (drug 4 esters of ciprofloxacin were synthesized under mixed phase conditions and by microwave excitation. The formation of ester derivatives of ciprofloxacin modified important molecular properties such as Log P and polar surface area which improves tissue penetration, yet preserved strong antibacterial activity. The Log P values for drugs 1, 2, 3, and 4 became −0.701, 0.437, 1.50, and 3.02, respectively. The polar surface areas for drugs 1, 2, 3, and 4 were determined to be 74.6 Angstroms2, 63.6 Angstroms2, 63.6 Angstroms2, and 63.6 Angstroms2, respectively. These values of Log P and polar surface area improved tissue penetration, as indicated by the determination of dermal permeability coefficient (Kp and subsequently into the superficial fascial layer. All drugs induced greater than 60% bacterial cell death at concentrations less than 1.0 micrograms/milliliter. The ester derivatives of ciprofloxacin showed strong antibacterial activity toward penicillin resistant E. coli.

  2. [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.

  3. The Effect of the Wastewater of Penicillin and Amoxicillin on the Antioxidant Indexes of Limnodrilus Hoffmeisteri

    Science.gov (United States)

    Dong, Yuxin; Shen, Hongyan

    2018-01-01

    In order to obtain some basic data for ecological risk assessment, an exposure experiment was carried out to study the effect of different volume of mixed penicillin and amoxicillin wastewater on Superoxide Dismutase (SOD) and Malondialdehyde (MDA) in Limnodrilus hoffmeisteri. Limnodrilus hoffmeisteri was exposed to different volume (10%, 20%, 30%, 40%, and 50%) of mixed wastewater for 15 days. According to the experimental data, the MDA contents and SOD activities in Limnodrilus hoffmeisteri muscle tissue had seen significant change significantly during the period of exposure. The results showed that the trend of SOD activities in low concentration groups (10% and 20%) increased at first, then decreased and increased at last. As exposure concentration increased (40% and 50%), SOD activities were inhibited in the early days (3 d), and was gradually induced in the later phase. The change of MDA content in muscle tissue of Limnodrilus hoffmeisteri was further investigated. It was found to be negatively correlated with the activity of SOD, and the high concentration group (50%) was in a remarkable induction state and reached the maximum at 6 d. According to the experimental data, the MDA contents and SOD activities in Limnodrilus hoffmeisteri muscle tissue had changed significantly and caused the oxidative damage.

  4. Functional redundancy of division specific penicillin-binding proteins in Bacillus subtilis.

    Science.gov (United States)

    Sassine, Jad; Xu, Meizhu; Sidiq, Karzan R; Emmins, Robyn; Errington, Jeff; Daniel, Richard A

    2017-10-01

    Bacterial cell division involves the dynamic assembly of a diverse set of proteins that coordinate the invagination of the cell membrane and synthesis of cell wall material to create the new cell poles of the separated daughter cells. Penicillin-binding protein PBP 2B is a key cell division protein in Bacillus subtilis proposed to have a specific catalytic role in septal wall synthesis. Unexpectedly, we find that a catalytically inactive mutant of PBP 2B supports cell division, but in this background the normally dispensable PBP 3 becomes essential. Phenotypic analysis of pbpC mutants (encoding PBP 3) shows that PBP 2B has a crucial structural role in assembly of the division complex, independent of catalysis, and that its biochemical activity in septum formation can be provided by PBP 3. Bioinformatic analysis revealed a close sequence relationship between PBP 3 and Staphylococcus aureus PBP 2A, which is responsible for methicillin resistance. These findings suggest that mechanisms for rescuing cell division when the biochemical activity of PBP 2B is perturbed evolved prior to the clinical use of β-lactams. © 2017 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

  5. Effect of mass transfer in a recirculation batch reactor system for immobilized penicillin amidase.

    Science.gov (United States)

    Park, J M; Choi, C Y; Seong, B L; Han, M H

    1982-10-01

    The effect of external mass transfer resistance on the overall reaction rate of the immobilized whole cell penicillin amidase of E. coli in a recirculation batch reactor was investigated. The internal diffusional resistance was found negligible as indicated by the value of effectiveness factor, 0.95. The local environmental change in a column due to the pH drop was successfully overcome by employing buffer solution. The reaction rate was measured by pH-stat method and was found to follow the simple Michaelis-Menten law at the initial stage of the reaction. The values of the net reaction rate experimentally determined were used to calculate the substrate concentration at the external surface of the catalyst pellet and then to calculate the mass transfer coefficient, k(L), at various flow rates and substrate concentrations. The correlation proposed by Chilton and Colburn represented adequately the experimental data. The linear change of log j(D) at low log N(Re) with negative slope was ascribed to the fact that the external mass transfer approached the state of pure diffusion in the limit of zero superficial velocity.

  6. Effect of Ampicillin, Streptomycin, Penicillin and Tetracycline on Metal Resistant and Non-Resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Dagmar Chudobova

    2014-03-01

    Full Text Available There is an arising and concerning issue in the field of bacterial resistance, which is confirmed by the number of deaths associated with drug-resistant bacterial infections. The aim of this study was to compare the effects of antibiotics on Staphylococcus aureus non-resistant strain and strains resistant to cadmium or lead ions. Metal resistant strains were created by the gradual addition of 2 mM solution of metal ions (cadmium or lead to the S. aureus culture. An increasing antimicrobial effect of ampicillin, streptomycin, penicillin and tetracycline (0, 10, 25, 50, 75, 150, 225 and 300 µM on the resistant strains was observed using a method of growth curves. A significant growth inhibition (compared to control of cadmium resistant cells was observed in the presence of all the four different antibiotics. On the other hand, the addition of streptomycin and ampicillin did not inhibit the growth of lead resistant strain. Other antibiotics were still toxic to the bacterial cells. Significant differences in the morphology of cell walls were indicated by changes in the cell shape. Our data show that the presence of metal ions in the urban environment may contribute to the development of bacterial strain resistance to other substances including antibiotics, which would have an impact on public health.

  7. Effect of Ampicillin, Streptomycin, Penicillin and Tetracycline on Metal Resistant and Non-Resistant Staphylococcus aureus

    Science.gov (United States)

    Chudobova, Dagmar; Dostalova, Simona; Blazkova, Iva; Michalek, Petr; Ruttkay-Nedecky, Branislav; Sklenar, Matej; Nejdl, Lukas; Kudr, Jiri; Gumulec, Jaromir; Tmejova, Katerina; Konecna, Marie; Vaculovicova, Marketa; Hynek, David; Masarik, Michal; Kynicky, Jindrich; Kizek, Rene; Adam, Vojtech

    2014-01-01

    There is an arising and concerning issue in the field of bacterial resistance, which is confirmed by the number of deaths associated with drug-resistant bacterial infections. The aim of this study was to compare the effects of antibiotics on Staphylococcus aureus non-resistant strain and strains resistant to cadmium or lead ions. Metal resistant strains were created by the gradual addition of 2 mM solution of metal ions (cadmium or lead) to the S. aureus culture. An increasing antimicrobial effect of ampicillin, streptomycin, penicillin and tetracycline (0, 10, 25, 50, 75, 150, 225 and 300 µM) on the resistant strains was observed using a method of growth curves. A significant growth inhibition (compared to control) of cadmium resistant cells was observed in the presence of all the four different antibiotics. On the other hand, the addition of streptomycin and ampicillin did not inhibit the growth of lead resistant strain. Other antibiotics were still toxic to the bacterial cells. Significant differences in the morphology of cell walls were indicated by changes in the cell shape. Our data show that the presence of metal ions in the urban environment may contribute to the development of bacterial strain resistance to other substances including antibiotics, which would have an impact on public health. PMID:24651395

  8. 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.

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

    Science.gov (United States)

    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.

  10. 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.

  11. Classification of Beta-lactamases and penicillin binding proteins using ligand-centric network models.

    Directory of Open Access Journals (Sweden)

    Hakime Öztürk

    Full Text Available β-lactamase mediated antibiotic resistance is an important health issue and the discovery of new β-lactam type antibiotics or β-lactamase inhibitors is an area of intense research. Today, there are about a thousand β-lactamases due to the evolutionary pressure exerted by these ligands. While β-lactamases hydrolyse the β-lactam ring of antibiotics, rendering them ineffective, Penicillin-Binding Proteins (PBPs, which share high structural similarity with β-lactamases, also confer antibiotic resistance to their host organism by acquiring mutations that allow them to continue their participation in cell wall biosynthesis. In this paper, we propose a novel approach to include ligand sharing information for classifying and clustering β-lactamases and PBPs in an effort to elucidate the ligand induced evolution of these β-lactam binding proteins. We first present a detailed summary of the β-lactamase and PBP families in the Protein Data Bank, as well as the compounds they bind to. Then, we build two different types of networks in which the proteins are represented as nodes, and two proteins are connected by an edge with a weight that depends on the number of shared identical or similar ligands. These models are analyzed under three different edge weight settings, namely unweighted, weighted, and normalized weighted. A detailed comparison of these six networks showed that the use of ligand sharing information to cluster proteins resulted in modules comprising proteins with not only sequence similarity but also functional similarity. Consideration of ligand similarity highlighted some interactions that were not detected in the identical ligand network. Analysing the β-lactamases and PBPs using ligand-centric network models enabled the identification of novel relationships, suggesting that these models can be used to examine other protein families to obtain information on their ligand induced evolutionary paths.

  12. Improving Clinical Outcomes in Patients With Methicillin-Sensitive Staphylococcus aureus Bacteremia and Reported Penicillin Allergy.

    Science.gov (United States)

    Blumenthal, Kimberly G; Parker, Robert A; Shenoy, Erica S; Walensky, Rochelle P

    2015-09-01

    Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection. First-line MSSA therapies (nafcillin, oxacillin, cefazolin) are generally avoided in the 10% of patients reporting penicillin (PCN) allergy, but most of these patients are not truly allergic. We used a decision tree with sensitivity analyses to determine the optimal evaluation and treatment for patients with MSSA bacteremia and reported PCN allergy. Our model simulates 3 strategies: (1) no allergy evaluation, give vancomycin (Vanc); (2) allergy history-guided treatment: if history excludes anaphylactic features, give cefazolin (Hx-Cefaz); and (3) complete allergy evaluation with history-appropriate PCN skin testing: if skin test negative, give cefazolin (ST-Cefaz). Model outcomes included 12-week MSSA cure, recurrence, and death; allergic reactions including major, minor, and potentially iatrogenic; and adverse drug reactions. Vanc results in the fewest patients achieving MSSA cure and the highest rate of recurrence (67.3%/14.8% vs 83.4%/9.3% for Hx-Cefaz and 84.5%/8.9% for ST-Cefaz) as well as the greatest frequency of allergic reactions (3.0% vs 2.4% for Hx-Cefaz and 1.7% for ST-Cefaz) and highest rates of adverse drug reactions (5.2% vs 4.6% for Hx-Cefaz and 4.7% for ST-Cefaz). Even in a "best case for Vanc" scenario, Vanc yields the poorest outcomes. ST-Cefaz is preferred to Hx-Cefaz although sensitive to input variations. Patients with MSSA bacteremia and a reported PCN allergy should have the allergy addressed for optimal treatment. Full allergy evaluation with skin testing seems to be preferred, although more data are needed. © The Author 2015. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Characterization of dacC, which encodes a new low-molecular-weight penicillin-binding protein in Bacillus subtilis

    DEFF Research Database (Denmark)

    Pedersen, Lotte Bang; Murray, T; Popham, D L

    1998-01-01

    The pbp gene (renamed dacC), identified by the Bacillus subtilis genome sequencing project, encodes a putative 491-residue protein with sequence homology to low-molecular-weight penicillin-binding proteins. Use of a transcriptional dacC-lacZ fusion revealed that dacC expression (i) is initiated...... at the end of stationary phase; (ii) depends strongly on transcription factor sigmaH; and (iii) appears to be initiated from a promoter located immediately upstream of yoxA, a gene of unknown function located upstream of dacC on the B. subtilis chromosome. A B. subtilis dacC insertional mutant grew...

  17. Proteomic analysis of the signaling pathway mediated by the heterotrimeric G? protein Pga1 of Penicillium chrysogenum

    OpenAIRE

    Carrasco-Navarro, Ulises; Vera-Estrella, Rosario; Barkla, Bronwyn J.; Z??iga-Le?n, Eduardo; Reyes-Vivas, Horacio; Fern?ndez, Francisco J.; Fierro, Francisco

    2016-01-01

    Background The heterotrimeric G? protein Pga1-mediated signaling pathway regulates the entire developmental program in Penicillium chrysogenum, from spore germination to the formation of conidia. In addition it participates in the regulation of penicillin biosynthesis. We aimed to advance the understanding of this key signaling pathway using a proteomics approach, a powerful tool to identify effectors participating in signal transduction pathways. Results Penicillium chrysogenum mutants with ...

  18. A Rapid and Sensitive Assay for the Detection of Benzylpenicillin (PenG in Milk.

    Directory of Open Access Journals (Sweden)

    Anna Pennacchio

    Full Text Available Antibiotics, such as benzyl-penicillin (PenG and cephalosporin, are the most common compounds used in animal therapy. Their massive and illegal use in animal therapy and prophylaxis inevitably causes the presence of traces in foods of animal origin (milk and meat, which creates several problems for human health. With the aim to prevent the negative impact of β-lactam and, in particular, PenG residues present in the milk on customer health, many countries have established maximum residue limits (MRLs. To cope with this problem here, we propose an effective alternative, compared to the analytical methods actually employed, to quantify the presence of penicillin G using the surface plasmon resonance (SPR method. In particular, the PenG molecule was conjugated to a protein carrier to immunize a rabbit and produce polyclonal antibodies (anti-PenG. The produced antibodies were used as molecular recognition elements for the design of a competitive immune-assay for the detection of PenG by SPR experiments. The detection limit of the developed assay was found to be 8.0 pM, a value much lower than the MRL of the EU regulation limit that is fixed at 12 nM. Thus, our results clearly show that this system could be successfully suitable for the accurate and easy determination of PenG.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. Co-ordinate synthesis and protein localization in a bacterial organelle by the action of a penicillin-binding-protein.

    Science.gov (United States)

    Hughes, H Velocity; Lisher, John P; Hardy, Gail G; Kysela, David T; Arnold, Randy J; Giedroc, David P; Brun, Yves V

    2013-12-01

    Organelles with specialized form and function occur in diverse bacteria. Within the Alphaproteobacteria, several species extrude thin cellular appendages known as stalks, which function in nutrient uptake, buoyancy and reproduction. Consistent with their specialization, stalks maintain a unique molecular composition compared with the cell body, but how this is achieved remains to be fully elucidated. Here we dissect the mechanism of localization of StpX, a stalk-specific protein in Caulobacter crescentus. Using a forward genetics approach, we identify a penicillin-binding-protein, PbpC, which is required for the localization of StpX in the stalk. We show that PbpC acts at the stalked cell pole to anchor StpX to rigid components of the outer membrane of the elongating stalk, concurrent with stalk synthesis. Stalk-localized StpX in turn functions in cellular responses to copper and zinc, suggesting that the stalk may contribute to metal homeostasis in Caulobacter. Together, these results identify a novel role for a penicillin-binding-protein in compartmentalizing a bacterial organelle it itself helps create, raising the possibility that cell wall-synthetic enzymes may broadly serve not only to synthesize the diverse shapes of bacteria, but also to functionalize them at the molecular level. © 2013 John Wiley & Sons Ltd.

  5. Elimination of Isoxazolyl-Penicillins antibiotics in waters by the ligninolytic native Colombian strain Leptosphaerulina sp. considerations on biodegradation process and antimicrobial activity removal.

    Science.gov (United States)

    Copete-Pertuz, Ledys S; Plácido, Jersson; Serna-Galvis, Efraím A; Torres-Palma, Ricardo A; Mora, Amanda

    2018-07-15

    In this work, Leptosphaerulina sp. (a Colombian native fungus) significantly removed three Isoxazolyl-Penicillin antibiotics (IP): oxacillin (OXA, 16000 μg L -1 ), cloxacillin (CLX, 17500 μg L -1 ) and dicloxacillin (DCX, 19000 μg L -1 ) from water. The biological treatment was performed at pH 5.6, 28 °C, and 160 rpm for 15 days. The biotransformation process and lack of toxicity of the final solutions (antibacterial activity (AA) and cytotoxicity) were tested. The role of enzymes in IP removal was analysed through in vitro studies with enzymatic extracts (crude and pre-purified) from Leptosphaerulina sp., commercial enzymes and enzymatic inhibitors. Furthermore, the applicability of mycoremediation process to a complex matrix (simulated hospital wastewater) was evaluated. IP were considerably abated by the fungus, OXA was the fastest degraded (day 6), followed by CLX (day 7) and DCX (day 8). Antibiotics biodegradation was associated to laccase and versatile peroxidase action. Assays using commercial enzymes (i.e. laccase from Trametes versicolor and horseradish peroxidase) and inhibitors (EDTA, NaCl, sodium acetate, manganese (II) ions) confirmed the significant role of enzymatic transformation. Whereas, biomass sorption was not an important process in the antibiotics elimination. Evaluation of AA against Staphylococcus aureus ATCC 6538 revealed that Leptosphaerulina sp. also eliminated the AA. In addition, the cytotoxicity assay (MTT) on the HepG2 cell line demonstrated that the IP final solutions were non-toxic. Finally, Leptosphaerulina sp. eliminated OXA and its AA from synthetic hospital wastewater at 6 days. All these results evidenced the potential of Leptosphaerulina sp. mycoremediation as a novel environmentally friendly process for the removal of IP from aqueous systems. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Evaluation of Penicillin Binding Protein 2a Latex Agglutination Assay for Identification of Methicillin-Resistant Staphylococcus aureus Directly from Blood Cultures

    OpenAIRE

    Chapin, Kimberle C.; Musgnug, Michael C.

    2004-01-01

    The penicillin binding protein 2a (PBP2a) latex agglutination test using a blood culture pellet was compared to the oxacillin screen agar method using isolated colonies. For blood cultures positive for Staphylococcus aureus (n = 70), the direct PBP2a test was 18% sensitive and 100% specific. The PBP2a test shows poor sensitivity when used directly with positive blood cultures.

  7. Direct detection of methicillin resistance in Staphylococcus aureus in blood culture broth by use of a penicillin binding protein 2a latex agglutination test.

    Science.gov (United States)

    Qian, Qinfang; Venkataraman, Lata; Kirby, James E; Gold, Howard S; Yamazumi, Toshiaki

    2010-04-01

    We studied the utility of performing a penicillin binding protein 2a latex agglutination (PBP-LA) assay directly on Bactec blood culture broth samples containing Staphylococcus aureus to rapidly detect methicillin resistance. The sensitivity, specificity, positive predictive value, and negative predictive value of this method were 94.1%, 97.5%, 98%, and 92.9%, respectively.

  8. Direct Detection of Methicillin Resistance in Staphylococcus aureus in Blood Culture Broth by Use of a Penicillin Binding Protein 2a Latex Agglutination Test▿

    OpenAIRE

    Qian, Qinfang; Venkataraman, Lata; Kirby, James E.; Gold, Howard S.; Yamazumi, Toshiaki

    2010-01-01

    We studied the utility of performing a penicillin binding protein 2a latex agglutination (PBP-LA) assay directly on Bactec blood culture broth samples containing Staphylococcus aureus to rapidly detect methicillin resistance. The sensitivity, specificity, positive predictive value, and negative predictive value of this method were 94.1%, 97.5%, 98%, and 92.9%, respectively.

  9. 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)

  10. 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.

  11. 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)

  12. Spontaneous nisin-resistant Listeria monocytogenes mutants with increased expression of a putative penicillin-binding protein and their sensitivity to various antibiotics

    DEFF Research Database (Denmark)

    Gravesen, Anne; Sorensen, K.; Aarestrup, Frank Møller

    2001-01-01

    -molecular-weight penicillin-binding proteins (PBPs), a histidine protein kinase, a protein of unknown function, and ClpB (putative functions from homology), The three former proteins had increased expression in a total of six out of 10 independent mutants originating from five different wildtype strains, indicating...

  13. PENICILLIN-BINDING PROTEIN 2X OF STREPTOCOCCUS-PNEUMONIAE - EXPRESSION IN ESCHERICHIA-COLI AND PURIFICATION OF A SOLUBLE ENZYMATICALLY ACTIVE DERIVATIVE

    NARCIS (Netherlands)

    LAIBLE, G; KECK, W; LURZ, R; MOTTL, H; FRERE, JM; JAMIN, M; HAKENBECK, R

    1992-01-01

    A 2.5-kb DNA fragment including the structural gene coding for the penicillin-binding protein 2x (PBP 2x) of Streptococcus pneumoniae has been cloned into the vector pJDC9 and expressed in Escherichia coli. Mapping of RNA polymerase binding sites by electron microscopy indicated that the pbpX

  14. 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.

  15. Radiocomplexation and biological evaluation of nemonoxacin in mice infected with multiresistant Staphylococcus aureus and penicillin-resistant Streptococci

    International Nuclear Information System (INIS)

    El-Kawy, O.A.; Farah, K.

    2015-01-01

    In the current investigation nemonoxacin (NMX) was radiolabeled with 99m Tc in the presence of stannous chloride dihydrate as reducing agent. Factors affecting the percent labeling yield of 99m Tc-Nemonoxacin ( 99m Tc-NMX) complex were studied in details. The labeled compound was radiochemically characterized and was stable for a time up to 4 h. The complex showed in vitro saturated binding with living multiresistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococci (PRSC). Biodistribution and imaging studies were performed. All results showed that 99m Tc-NMX complex is a promising agent for MRSA and PRSC infection imaging and can differentiate between infected and sterile inflammations. (author)

  16. Labelling of penicillin-binding proteins from Escherichia coli with photoreactive derivatives of #betta#-lactam antibiotics

    International Nuclear Information System (INIS)

    Aran, V.; Rodriguez-Tebar, A.; Vazquez, D.

    1983-01-01

    The authors have synthesized a number of photoreactive radiolabelled #betta#-lactams that react and form permanent covalent bonds with the penicillin-binding proteins (PBPs), since photoreactive ligand derivatives have been used to some extent for structural studies on membranes and other biological structures. Chemical and photochemical labelling of a receptor by its ligand are important techniques to elucidate the nature of the ligand-receptor interaction, and for identification and characterization of receptors. They have synthesized two #betta#-lactam derivatives each containing two different photoreactive moieties. One of them is an aryl azido compound, widely known as a photoreactive reagent for labelling studies, whereas the other one contains a nitroguaiacol derived group used in photochemical studies with other biological materials. (Auth.)

  17. Structural basis of metallo-β-lactamase, serine-β-lactamase and penicillin-binding protein inhibition by cyclic boronates

    Science.gov (United States)

    Brem, Jürgen; Cain, Ricky; Cahill, Samuel; McDonough, Michael A.; Clifton, Ian J.; Jiménez-Castellanos, Juan-Carlos; Avison, Matthew B.; Spencer, James; Fishwick, Colin W. G.; Schofield, Christopher J.

    2016-08-01

    β-Lactamases enable resistance to almost all β-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as `transition state analogue' inhibitors of nucleophilic serine enzymes, including serine-β-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent β-lactamases by a mechanism involving mimicking of the common tetrahedral intermediate. Cyclic boronates also potently inhibit the non-essential penicillin-binding protein PBP 5 by the same mechanism of action. The results open the way for development of dual action inhibitors effective against both serine- and metallo-β-lactamases, and which could also have antimicrobial activity through inhibition of PBPs.

  18. Prospective, multicenter clinical trial to validate new products for skin tests in the diagnosis of allergy to penicillin.

    Science.gov (United States)

    Fernández, J; Torres, M J; Campos, J; Arribas-Poves, F; Blanca, M

    2013-01-01

    Allergy to penicillin is the most commonly reported type of drug hypersensitivity. Diagnosis is currently confirmed using skin tests with benzylpenicillin reagents, ie, penicilloyl-polylysine (PPL) as the major determinant of benzylpenicillin and benzylpenicillin, benzylpenicilloate and benzylpenilloate as a minor determinant mixture (MDM). To synthesize and assess the diagnostic capacity of 2 new benzylpenicillin reagents in patients with immediate hypersensitivity reactions to B-lactams: benzylpenicilloyl octa-L-lysine (BP-OL) as the major determinant and benzylpenilloate (penilloate) as the minor determinant. Prospective multicenter clinical trial performed in 18 Spanish centers. Efficacy was assessed by detection of positive skin test results in an allergic population and negative skin test results in a nonallergic, drug-exposed population. Sensitivity, specificity, and negative and positive predictive values were determined. The study sample comprised 94 allergic patients: 31 (35.23%) presented anaphylaxis, 4 (4.55%) anaphylactic shock, 51 (58.04%) urticaria, and 2 (2.27%) no specific condition. The culprit 8-lactams were amoxicillin in 63 cases (71.60%), benzypencillin in 14 cases (15.89%), cephalosporins in 2 cases (2.27%), other drugs in 3 cases (3.42%), and unidentified agents in 6 cases (6.82%). The results of testing with BP-OL were positive in 46 cases (52.3%); the results of testing with penilloate were positive in 33 cases (37.5%). When both reagents were taken into consideration, sensitivity reached 61.36% and specificity 100%. Skin testing with penilloate was significantly more often negative when the interval between the reaction and the study was longer. The sensitivity of BP-OL and penilloate was 61%. Considering that amoxicillin was the culprit drug in 71% of reactions, these results indicate that most patients were allergic to the whole group of penicillins. These data support the use of benzylpenicillin determinants in the diagnosis of allergy

  19. A simple, low-cost and robust capillary zone electrophoresis Method with capacitively coupled contactless conductivity detection for the routine determination of four selected penicillins in Money-constrained laboratories

    NARCIS (Netherlands)

    Paul, Prasanta; Sänger-van de Griend, Cari; Adams, Erwin; Van Schepdael, Ann

    2018-01-01

    A simple and robust capillary zone electrophoresis Method was developed and validated for the determination of amoxicillin and clavulanate, ampicillin, phenoxymethyl penicillin (Pen V) as well as flucloxacillin. Capacitively coupled contactless conductivity detection was employed as detection Mode

  20. 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.

  1. 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

  2. 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.

  3. [Contribution of microbiologists of Kirov City to development of penicillin and streptomycin production processes (70 years since development of technology for submerged production of first domestic antibiotics)].

    Science.gov (United States)

    Bakulin, M K; Tumanov, A S; Bakulin, V M; Kalininskiĭ, V B

    2014-01-01

    The publication is concerned with development of the technological processes for submered production of the first domestic antibiotics 70 years age. The literature data on the contribution of the microbiologists of the Kirov City and mainly the workers of the Red Army Research Institute of Epidemiology and Hygiene (nowadays Central Research Institute No. 48 of the Ministry of Defense of the Russian Federation, Kirov), to development of the manufacture processes for production of penicillin and streptomycin are reviewed.

  4. 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.

  5. Analysis of the interactions between human serum albumin/amphiphilic penicillin in different aqueous media: an isothermal titration calorimetry and dynamic light scattering study

    International Nuclear Information System (INIS)

    Barbosa, Silvia; Taboada, Pablo; Mosquera, Victor

    2005-01-01

    The complexation process of the amphiphilic penicillins sodium cloxacillin and sodium dicloxacillin with the protein human serum albumin (HSA) in aqueous buffered solutions of pH 4.5 and 7.4 at 25 o C was investigated through isothermal titration calorimetry (ITC) and dynamic light scattering. ITC experiments were carried out in the very dilute regime and showed that although hydrophobic interactions are the leading forces for complexation, electrostatic interactions also play an important role. The possibility of the formation of hydrogen bonds is also deduced from experimental data. The thermodynamic quantities of the binding mechanism, i.e, the enthalpy, ΔHITCi, entropy, ΔSITCi, Gibbs energy, ΔGITCi, binding constant, KITCi and the number of binding sites, n i , were obtained. The binding was saturable and is characterised by Langmuir adsorption isotherms. From ITC data and following a theoretical model, the number of bound and free penicillin molecules was calculated. From Scatchard plots, KITCi and n i were obtained and compared with those from ITC data. The interaction potential between the HSA-penicillin complexes and their stability were determined at pH 7.4 from the dependence of the diffusion coefficients on protein concentration by application of the DLVO colloidal stability theory. The results indicate decreasing stability of the colloidal dispersion of the drug-protein complexes with increase in the concentration of added drug

  6. Old Drugs To Treat Resistant Bugs: Methicillin-Resistant Staphylococcus aureus Isolates with mecC Are Susceptible to a Combination of Penicillin and Clavulanic Acid.

    Science.gov (United States)

    Ba, Xiaoliang; Harrison, Ewan M; Lovering, Andrew L; Gleadall, Nicholas; Zadoks, Ruth; Parkhill, Julian; Peacock, Sharon J; Holden, Matthew T G; Paterson, Gavin K; Holmes, Mark A

    2015-12-01

    β-Lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) is mediated by the expression of an alternative penicillin-binding protein 2a (PBP2a) (encoded by mecA) with a low affinity for β-lactam antibiotics. Recently, a novel variant of mecA, known as mecC, was identified in MRSA isolates from both humans and animals. In this study, we demonstrate that mecC-encoded PBP2c does not mediate resistance to penicillin. Rather, broad-spectrum β-lactam resistance in MRSA strains carrying mecC (mecC-MRSA strains) is mediated by a combination of both PBP2c and the distinct β-lactamase encoded by the blaZ gene of strain LGA251 (blaZLGA251), which is part of mecC-encoding staphylococcal cassette chromosome mec (SCCmec) type XI. We further demonstrate that mecC-MRSA strains are susceptible to the combination of penicillin and the β-lactam inhibitor clavulanic acid in vitro and that the same combination is effective in vivo for the treatment of experimental mecC-MRSA infection in wax moth larvae. Thus, we demonstrate how the distinct biological differences between mecA- and mecC-encoded PBP2a and PBP2c have the potential to be exploited as a novel approach for the treatment of mecC-MRSA infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. PASTA in Penicillin Binding Proteins and Serine/Threonine Kinases: A Recipe of Structural, Dynamic and Binding Properties.

    Science.gov (United States)

    Calvanese, Luisa; Falcigno, Lucia; Squeglia, Flavia; D'Auria, Gabriella; Berisio, Rita

    2017-11-24

    Penicillin binding proteins (PBPs) and Serine Threonine kinases (STPKs) are two classes of bacterial enzymes whose involvement in a series of vital processes in bacterial growth and division is well assessed. Many PBPs and STPKs show linked an ancillary domain named PASTA, whose functional role is not completely deciphered so far. It has been proposed that PASTAs are sensor modules that by binding opportune ligands (i.e. muropeptides) activate the cognate proteins to their functions. However, based on recent data, the sensor annotation sounds true for PASTA from STPKs, and false for PASTA from PBPs. Different PASTA domains, belonging or not to different protein classes, sharing or not appreciable sequence identities, always show identical folds. This survey of the structural, binding and dynamic properties of PASTA domains pursues the reasons why identical topologies may turn in different roles. Amino acid compositions, total charges and distribution of the hydrophobic/hydrophilic patches on the surface, significantly vary among PASTAs from STPKs and PBPs and appear to correlate with different functions. A possible criterion to discriminate between PASTA modules of STPKs or PBPs solely based on their sequences is proposed. Possibly reflecting different species as well as functional roles and evolutionary profile, our routine represents a fast even though approximate method to distinguish between PASTA belonging to different classes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Lactobacillus rhamnosus GG Intake Modifies Preschool Children's Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use.

    Directory of Open Access Journals (Sweden)

    Katri Korpela

    Full Text Available Antibiotic use is considered among the most severe causes of disturbance to children's developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children's microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children's antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2-7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use.ClinicalTrials.gov NCT01014676.

  9. Latin-American Co-operation in Biotechnology Programme: Industrial penicillin amidase for 6 amino penicillanic acid production

    Directory of Open Access Journals (Sweden)

    Dolly Montoya C.

    2001-07-01

    Full Text Available This work evaluates technological and economic transference related to the Production of Penicillin Amidase for use in 6 Amine Penicillanic acid (6-APA Production Project, wich is a part of the United Nations1 Regional Biotechnology Programme for Latin America and the Caribbean. This paper analyses the evolution of international cooperation by looking at the project's development. The methodology used includes analysis of: the project's development; participant and budgetary goals; results; copyright; project conditions; and sale of biocatalyst and 6-APA. All technical objectives were achieved; international co-operation, as well as co-operation between Industry and University were successful. Technological transference to the pilot plant was effective; many students involved in the project were simultaneously taking M.Sc. and Ph.D's courses. Nevertheless, neither the technology necessary for the biocatalyst's manufacture nor the biocatalyst itself were used. Analysis of the project has provided some orientation concerning those internal and external problems which arose during the development and sale of biotechnology in our countries and has tried to propose some alternatives for taking advantage of international co-operation.

  10. 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.

  11. Rapid Treponema pallidum clearance from blood and ulcer samples following single dose benzathine penicillin treatment of early syphilis.

    Science.gov (United States)

    Tipple, Craig; Jones, Rachael; McClure, Myra; Taylor, Graham

    2015-02-01

    Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum), is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene) and RNA (16S rRNA) quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53). The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84). From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08 x 107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20-56) after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies.

  12. Perianesthetic refractory anaphylactic shock with cefuroxime in a patient with history of penicillin allergy on multiple antihypertensive medications

    Directory of Open Access Journals (Sweden)

    Deb Sanjay Nag

    2017-03-01

    Full Text Available We report a case of perianesthetic refractory anaphylactic shock with cefuroxime in a patient with history of penicillin allergy on regular therapy with atenolol, losartan, prazosin and nicardipine. Severe anaphylactic shock was only transiently responsive to 10 mL of (1:10,000 epinephrine and needed norepinephrine and dopamine infusion. Supportive therapy with vasopressors and inotropes along with mechanical ventilation for the next 24 hours resulted in complete recovery. She was successfully operated upon 2 weeks later with the same anesthetic drugs but intravenous ciprofloxacin as the alternative antibiotic for perioperative prophylaxis. Resumo: Relatamos um caso de choque anafilático refratário no período perianestésico com cefuroxima em paciente com história de alergia à penicilina em terapia regular com atenolol, losartan, prazosina e nicardipine. O choque anafilático grave foi apenas transitoriamente responsivo a 10 mL de epinefrina (1:10000 e precisou de infusão de norepinefrina e dopamina. A terapia de apoio com vasopressores e inotrópicos, juntamente com ventilação mecânica por 24 horas resultaram em recuperação completa. A paciente foi operada com sucesso duas semanas mais tarde, com os mesmos agentes anestésicos, mas com ciprofloxacina intravenosa como antibiótico alternativo para a profilaxia perioperatória. Keywords: Anaphylaxis, Perianesthetic, Cefuroxime, Palavras-chave: Anafilaxia, Perianestésico, Cefuroxima

  13. Penicillin-Binding Protein Transpeptidase Signatures for Tracking and Predicting β-Lactam Resistance Levels in Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Yuan Li

    2016-06-01

    Full Text Available β-Lactam antibiotics are the drugs of choice to treat pneumococcal infections. The spread of β-lactam-resistant pneumococci is a major concern in choosing an effective therapy for patients. Systematically tracking β-lactam resistance could benefit disease surveillance. Here we developed a classification system in which a pneumococcal isolate is assigned to a “PBP type” based on sequence signatures in the transpeptidase domains (TPDs of the three critical penicillin-binding proteins (PBPs, PBP1a, PBP2b, and PBP2x. We identified 307 unique PBP types from 2,528 invasive pneumococcal isolates, which had known MICs to six β-lactams based on broth microdilution. We found that increased β-lactam MICs strongly correlated with PBP types containing divergent TPD sequences. The PBP type explained 94 to 99% of variation in MICs both before and after accounting for genomic backgrounds defined by multilocus sequence typing, indicating that genomic backgrounds made little independent contribution to β-lactam MICs at the population level. We further developed and evaluated predictive models of MICs based on PBP type. Compared to microdilution MICs, MICs predicted by PBP type showed essential agreement (MICs agree within 1 dilution of >98%, category agreement (interpretive results agree of >94%, a major discrepancy (sensitive isolate predicted as resistant rate of <3%, and a very major discrepancy (resistant isolate predicted as sensitive rate of <2% for all six β-lactams. Thus, the PBP transpeptidase signatures are robust indicators of MICs to different β-lactam antibiotics in clinical pneumococcal isolates and serve as an accurate alternative to phenotypic susceptibility testing.

  14. 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

  15. G K Ananthasuresh

    Indian Academy of Sciences (India)

    G K Ananthasuresh · More Details Fulltext PDF. Volume 17 Issue 4 April 2012 pp 317-318 Editorial. Editorial · G K Ananthasuresh · More Details Fulltext PDF. Volume 20 Issue 2 February 2015 pp 98-122 General Article. Buckminster Fuller and his Fabulous Designs · G K Ananthasuresh · More Details Fulltext PDF ...

  16. 5G Spectrum Sharing

    OpenAIRE

    Nekovee, Maziar; Rudd, Richard

    2017-01-01

    In this paper an overview is given of the current status of 5G industry standards, spectrum allocation and use cases, followed by initial investigations of new opportunities for spectrum sharing in 5G using cognitive radio techniques, considering both licensed and unlicensed scenarios. A particular attention is given to sharing millimeter-wave frequencies, which are of prominent importance for 5G.

  17. G M Kalamse

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences. G M Kalamse. Articles written in Journal of Chemical Sciences. Volume 117 Issue 6 November 2005 pp 673-676. Dielectric studies of binary mixtures of -propyl alcohol and ethylenediamine · B S Narwade P G Gawali Rekha Pande G M Kalamse · More Details Abstract ...

  18. A new mechanism to render clinical isolates of Escherichia coli non-susceptible to imipenem: substitutions in the PBP2 penicillin-binding domain.

    Science.gov (United States)

    Aissa, Nejla; Mayer, Noémie; Bert, Fréderic; Labia, Roger; Lozniewski, Alain; Nicolas-Chanoine, Marie-Hélène

    2016-01-01

    So far, two types of mechanism are known to be involved in carbapenem non-susceptibility of Escherichia coli clinical isolates: reduced outer membrane permeability associated with production of ESBLs and/or overproduction of class C β-lactamases; and production of carbapenemases. Non-susceptibility to only imipenem observed in two clinical isolates suggested a new mechanism, described in the present study. The ST was determined for the two isolates of E. coli (strains LSNy and VSBj), and their chromosomal region encoding the penicillin-binding domain of PBP2 was amplified, sequenced and then used for recombination experiments in E. coli K12 C600. Antibiotic MICs were determined using the Etest method. Strains LSNy and VSBj, which displayed ST23 and ST345, respectively, showed amino acid substitutions in their PBP2 penicillin-binding domain. Substitution Ala388Ser located in motif 2 (SXD) was common to the two strains. Two additional substitutions (Ala488Thr and Leu573Val) located outside the two other motifs were identified in strain LSNy, whereas another one (Thr331Pro) located in motif 1 was identified in strain VSBj. Recombination experiments to reproduce non-susceptibility to imipenem in E. coli K12 C600 were not successful when only the common substitution was transferred, whereas recombination with DNA fragments including either the three substitutions (strain LSNy) or the two substitutions (strain VSBj) were successful. Substitution of amino acids in the penicillin-binding domain of PBP2 is a new mechanism by which E. coli clinical isolates specifically resist imipenem. © 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.

  19. Physico-Chemical-Managed Killing of Penicillin-Resistant Static and Growing Gram-Positive and Gram-Negative Vegetative Bacteria

    Science.gov (United States)

    Richmond, Robert Chaffee (Inventor); Schramm, Jr., Harry F. (Inventor); Defalco, Francis G. (Inventor); Farris, III, Alex F. (Inventor)

    2012-01-01

    Systems and methods for the use of compounds from the Hofmeister series coupled with specific pH and temperature to provide rapid physico-chemical-managed killing of penicillin-resistant static and growing Gram-positive and Gram-negative vegetative bacteria. The systems and methods represent the more general physico-chemical enhancement of susceptibility for a wide range of pathological macromolecular targets to clinical management by establishing the reactivity of those targets to topically applied drugs or anti-toxins.

  20. Rapid Treponema pallidum clearance from blood and ulcer samples following single dose benzathine penicillin treatment of early syphilis.

    Directory of Open Access Journals (Sweden)

    Craig Tipple

    2015-02-01

    Full Text Available Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum, is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene and RNA (16S rRNA quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53. The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84. From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08 x 107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20-56 after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies.

  1. Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients.

    Science.gov (United States)

    Aleman, Jacomien; Moojen, Dirk Jan F; van Ogtrop, Marc L; Poolman, Rudolf W; Franssen, Eric J F

    2018-01-01

    Objectives : Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections. In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections. Methods : A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l. Results : 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395). Conclusions : In our population of patients with OIRI long-term treatment with conventionally dosed

  2. G-warm inflation

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, Ramón, E-mail: ramon.herrera@pucv.cl [Instituto de Física, Pontificia Universidad Católica de Valparaíso, Avenida Brasil 2950, Casilla 4059, Valparaíso (Chile)

    2017-05-01

    A warm inflationary universe in the context of Galileon model or G-model is studied. Under a general formalism we study the inflationary dynamics and the cosmological perturbations considering a coupling of the form G (φ, X )= g (φ) X . As a concrete example, we consider an exponential potential together with the cases in which the dissipation and Galilean coefficients are constants. Also, we study the weak regime given by the condition R <1+3 gH φ-dot , and the strong regime in which 1< R +3 gH φ-dot . Additionally, we obtain constraints on the parameters during the evolution of G-warm inflation, assuming the condition for warm inflation in which the temperature T > H , the conditions or the weak and strong regimes, together with the consistency relation r = r ( n {sub s} ) from Planck data.

  3. Study on the efficacy of cefaclor for the treatment of asymptomatic bacteriuria and lower urinary tract infections in pregnant women with a history of hypersensitivity to penicillin.

    Science.gov (United States)

    Stamatiou, K; Alevizos, A; Petrakos, G; Lentzas, I; Papathanasiou, M; Mariolis, A; Panagopoulos, P; Sofras, F

    2007-01-01

    The purpose of this study was to compare the efficacy and safety profile of twice daily versus the conventional three daily intake of cefaclor administrated orally for five to seven days in the treatment of asymptomatic bacteriuria or acute cystitis in pregnant women with a history of hypersensitivity to penicillin. Between August 2003 and August 2004, 63 pregnant women with a positive urine culture and a history of suspicion of hypersensitivity to penicillin were randomly divided into two groups. The women in the first group received 500 mg of cefaclor while those in the second group received 750 mg of cefaclor for five to seven days. Laboratory and clinical results were assessed a week and a month after complettion of the therapy. Final therapy (bacteriologic eradication) succeeded in 93.7% (30/32) of the first group and in 90.3% (28/31) of the second group. Dosage of cefaclor at 750 mg is as effective as conventional cefaclor at 500 mg and better tolerated.

  4. Culture Negative Listeria monocytogenes Meningitis Resulting in Hydrocephalus and Severe Neurological Sequelae in a Previously Healthy Immunocompetent Man with Penicillin Allergy

    Directory of Open Access Journals (Sweden)

    Shahin Gaini

    2015-01-01

    Full Text Available 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 for bacteria, no bacterial growth, and negative polymerase chain reaction for bacterial DNA. The patient developed hydrocephalus on a second CT scan of the brain on the 5th day of admission. An external ventricular catheter was inserted and Listeria monocytogenes grew in the cerebrospinal fluid from 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 and inflammation even with negative microscopy, negative cultures, and negative broad range polymerase chain reaction in cases of Listeria meningitis. Follow-up spinal taps can be necessary to detect the presence of Listeria monocytogenes.

  5. Chlamydia trachomatis responds to heat shock, penicillin induced persistence, and IFN-gamma persistence by altering levels of the extracytoplasmic stress response protease HtrA

    Directory of Open Access Journals (Sweden)

    Mathews Sarah A

    2008-11-01

    Full Text Available Abstract Background Chlamydia trachomatis, an obligate intracellular human pathogen, is the most prevalent bacterial sexually transmitted infection worldwide and a leading cause of preventable blindness. HtrA is a virulence and stress response periplasmic serine protease and molecular chaperone found in many bacteria. Recombinant purified C. trachomatis HtrA has been previously shown to have both activities. This investigation examined the physiological role of Chlamydia trachomatis HtrA. Results The Chlamydia trachomatis htrA gene complemented the lethal high temperature phenotype of Escherichia coli htrA- (>42°C. HtrA levels were detected to increase by western blot and immunofluorescence during Chlamydia heat shock experiments. Confocal laser scanning microscopy revealed a likely periplasmic localisation of HtrA. During penicillin induced persistence of Chlamydia trachomatis, HtrA levels (as a ratio of LPS were initially less than control acute cultures (20 h post infection but increased to more than acute cultures at 44 h post infection. This was unlike IFN-γ persistence where lower levels of HtrA were observed, suggesting Chlamydia trachomatis IFN-γ persistence does not involve a broad stress response. Conclusion The heterologous heat shock protection for Escherichia coli, and increased HtrA during cell wall disruption via penicillin and heat shock, indicates an important role for HtrA during high protein stress conditions for Chlamydia trachomatis.

  6. 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.

  7. Antimicrobial susceptibility against penicillin, ampicillin and vancomycin of viridans group Streptococcus in oral microbiota of patients at risk of infective endocarditis.

    Science.gov (United States)

    Süzük, Serap; Kaşkatepe, Banu; Çetin, Mustafa

    2016-09-01

    The viridans group Streptococci (VGS) are most abundant in the mouth; in some instances they might emerge as pathogens particularly in infective endocarditis (IE). In this study, we aimed to define and determine the susceptibility against antibiotics of VGS that are members of the oral microbiota of patients exhibiting a risk of developing IE. Forty-nine patients at risk of infective endocarditis were included in the study. Identification of the bacteria was performed using API STREP (bioMérieux, France). Gradient test strips (E-Test, France) were used to determine MIC of the bacteria against penicillin, ampicillin, and vancomycin. The distribution of the isolated VGS groups was determined as follows: Streptococcus mitis 32.6% and anginosus group - 32.6%, S. sanguinis group - 16.3%, S. mutans group - 12.2%, and S. salivarius group - 6.1%. The rates of resistance and reduced sensitivity of the isolates for penicillin and ampicillin were determined at 61.2% and 55.1%, respectively. However, all isolates were found to be susceptible to vancomycin. We conclude that the antimicrobial resistance of VGS should be determined on a regular basis locally, and decisions on therapeutic and prophylactic interventions should be given taking this resistance into consideration.

  8. Prevalence of penicillin and erythromycin resistance among invasive Streptococcus pneumoniae isolates reported by laboratories in the southern and eastern Mediterranean region.

    Science.gov (United States)

    Borg, M A; Tiemersma, E; Scicluna, E; van de Sande-Bruinsma, N; de Kraker, M; Monen, J; Grundmann, H

    2009-03-01

    Information about the epidemiology of resistance in Streptococcus pneumoniae within southern and eastern countries of the Mediterranean region is incomplete, as reports have been sporadic and difficult to compare. Over a 36-month period, from 2003 to 2005, the ARMed project collected 1298 susceptibility test results of invasive isolates of S. pneumoniae from blood and spinal fluid cultures routinely processed within 59 participating laboratories situated in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. Overall, 26% (335) of isolates were reported as non-susceptible to penicillin, with the highest proportions being reported from Algeria (44%) and Lebanon (40%). During the same time period, the highest proportions of pneumococci that were not susceptible to erythromycin were reported from Malta (46%) and Tunisia (39%). Proportions of dual non-susceptibility in excess of 5% were found in laboratories in Algeria, Tunisia, Lebanon, Jordan and Turkey. ARMed data on the antimicrobial resistance epidemiology of S. pneumoniae in the southern and eastern Mediterranean region provided evidence of high rates of resistance, especially to penicillin. This evidence calls for a greater focus on the identification of relevant drivers of resistance and on the implemention of effective practices in order to address the problem of resistence.

  9. G U Kulkarni

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. G U Kulkarni. Articles written in Bulletin of Materials Science. Volume 24 Issue 5 October 2001 pp 515-521 Magnetic Materials. Submicron particles of Co, Ni and Co–Ni alloys · P Saravanan T A Jose P John Thomas G U Kulkarni · More Details Abstract Fulltext PDF. Magnetic ...

  10. G S Gupta

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. G S Gupta. Articles written in Bulletin of Materials Science. Volume 36 Issue 7 December 2013 pp 1323-1329. Structural characterization of electrodeposited boron · Ashish Jain C Ghosh T R Ravindran S Anthonysamy R Divakar E Mohandas G S Gupta · More Details Abstract ...

  11. P G Babu

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. P G Babu. Articles written in Resonance – Journal of Science Education. Volume 3 Issue 7 July 1998 pp 53-60 General Article. Game Theory - Nash Equilibrium · P G Babu · More Details Fulltext PDF. Volume 3 Issue 8 August 1998 pp 46-55 General Article.

  12. G Chandramohan Reddy

    Indian Academy of Sciences (India)

    Home; Journals; Sadhana. G Chandramohan Reddy. Articles written in Sadhana. Volume 36 Issue 2 April 2011 pp 223-249. In-plane anisotropy in tensile deformation and its influence on the drawability of Nimonic C–263 alloy sheets · K Ankamma D V V Satyanarayana G Chandramohan Reddy M Komaraiah N Eswara ...

  13. A G Samuelson

    Indian Academy of Sciences (India)

    Volume 5 Issue 1 January 2000 pp 101-104 Research News. More than a Handful...N5+ · A G Samuelson · More Details Fulltext PDF. Volume 5 Issue 5 May 2000 pp 64-66 General Article. Fulfilling Mendeleev's Dream · A G Samuelson · More Details Fulltext PDF. Volume 12 Issue 3 March 2007 pp 70-76 Feature Article.

  14. G Wayne Craig

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. G Wayne Craig. Articles written in Resonance – Journal of Science Education. Volume 19 Issue 7 July 2014 pp 624-640 General Article. Eschenmoser Approach to Vitamin B12 by A/D Strategy: An Unexpected Journey · G Wayne Craig · More Details Fulltext PDF ...

  15. G M Ballabh

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. G M Ballabh. Articles written in Resonance – Journal of Science Education. Volume 10 Issue 8 August 2005 pp 6-24 General Article. Dynamics of the Sun-Earth-Moon System · S M Alladin G M Ballabh · More Details Fulltext PDF ...

  16. G M Moremedi

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics. G M Moremedi. Articles written in Pramana – Journal of Physics. Volume 77 Issue 3 September 2011 pp 493-507. Effects of non-uniform interfacial tension in small Reynolds number flow past a spherical liquid drop · D P Mason G M Moremedi · More Details Abstract Fulltext ...

  17. G M Kulkerni

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. G M Kulkerni. Articles written in Resonance – Journal of Science Education. Volume 3 Issue 2 February 1998 pp 77-78 Classroom. Chemical Flag · G M Kulkerni · More Details Fulltext PDF ...

  18. M G Narasimhan

    Indian Academy of Sciences (India)

    Volume 2 Issue 2 February 1997 pp 4-4 Article-in-a-Box. The Popper-Kuhn Debate on the Nature of Scientific Development · M G Narasimhan · More Details Fulltext PDF. Volume 16 Issue 6 June 2011 pp 529-539 General Article. Kosambi's Vision of Science - A Critical Appreciation · M G Narasimhan · More Details Fulltext ...

  19. G K Suryaprakash

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. G K Suryaprakash. Articles written in Resonance – Journal of Science Education. Volume 22 Issue 12 December 2017 pp 1111-1153 General Article. George Andrew Olah: Across Conventional Lines · Ripudaman Malhotra Thomas Mathew G K Suryaprakash.

  20. G Srinivasa Murthy

    Indian Academy of Sciences (India)

    P Chaitanya Das G Srinivasa Murthy C P Gopalakrishnan P C Deshmukh · More Details Fulltext PDF. Volume 9 Issue 7 July 2004 pp 77-85 Classroom. Motion of Charged Particles in Electromagnetic Fields and Special Theory of Relativity · P Chaitanya Das G Srinivasa Murthy P C Deshmukh K Satish Kumar T A Venkatesh.

  1. H G Khorana

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. H G Khorana. Articles written in Resonance – Journal of Science Education. Volume 17 Issue 12 December 2012 pp 1174-1197 Classics. Total Synthesis of a Gene · H G Khorana · More Details Fulltext PDF ...

  2. Nocera, Prof. Daniel G

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 2013 Honorary. Nocera, Prof. Daniel G. Date of birth: 1957. Address: Dept. of Chemistry & Chem. Biol., Harvard University, 12, Oxford Street, Cambridge, MA 02138, USA Contact: Office: (+1-617) 495 8904. Email: dnocera@fas.harvard.edu. http://chemistry.harvard.edu/people/daniel-g-nocera.

  3. High Gravity (g) Combustion

    National Research Council Canada - National Science Library

    Zelina, Joseph

    2006-01-01

    .... The Ultra-Compact Combustor (UCC), a novel design based on trapped-vortex combustor (TVC) work that uses high swirl in a circumferential cavity to enhance reaction rates via high cavity g-loading on the order of 3000 g's...

  4. Z G Ghevariya

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Earth System Science. Z G Ghevariya. Articles written in Journal of Earth System Science. Volume 110 Issue 2 June 2001 pp 111-132. Geochemistry and magnetostratigraphy of Deccan flows at Anjar, Kutch · A D Shukla N Bhandari Sheela Kusumgar P N Shukla Z G Ghevariya K Gopalan V ...

  5. G-warm inflation

    Science.gov (United States)

    Herrera, Ramón

    2017-05-01

    A warm inflationary universe in the context of Galileon model or G-model is studied. Under a general formalism we study the inflationary dynamics and the cosmological perturbations considering a coupling of the form G(phi,X)=g(phi) X. As a concrete example, we consider an exponential potential together with the cases in which the dissipation and Galilean coefficients are constants. Also, we study the weak regime given by the condition RR+3gHdot phi. Additionally, we obtain constraints on the parameters during the evolution of G-warm inflation, assuming the condition for warm inflation in which the temperature T>H, the conditions or the weak and strong regimes, together with the consistency relation r=r(ns) from Planck data.

  6. 5G in Finland

    OpenAIRE

    Leinonen, Jami

    2017-01-01

    The thesis describes about 5G and studies what new it brings and how it is better than the previous telecommunication generation. Firstly, explains when 5G research began presents main user cases and how the new services, xMMB, mMTC and uMTC, will respond to these cases. After that, new concepts such as DyRAN, LSCP, Spectrum toolbox, D2D communication, mmW/cmW and massive MIMO systems are addressed. These all are 5G specific, and they all will provide more flexible systems to bring mobile com...

  7. The g-2 ring

    CERN Multimedia

    1974-01-01

    The precise measurement of "g-2", the anomalous magnetic moment of the muon, required a special muon storage ring with electrostatic focussing and very accurate knowledge of the magnetic bending field. For more details see under photo 7405430.

  8. G-AIRMET

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A G-AIRMET is a 3 hourly graphical forecast of en route weather hazards at intensities lower than those that require the issuance of a SIGMET.

  9. G S Taki

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics. G S Taki. Articles written in Pramana – Journal of Physics. Volume 59 Issue 5 November 2002 pp 775-780. 6.4 GHz ECR ion source at VECC · G S Taki D K Chakraborty R K Bhandari · More Details Abstract Fulltext PDF. The 6.4 GHz ECR ion source that was indigenously ...

  10. Direct detection of methicillin-resistant Staphylococcus aureus from blood cultures using an immunochromatographic immunoassay-based MRSA rapid kit for the detection of penicillin-binding protein 2a.

    Science.gov (United States)

    Shin, Kyeong Seob; Song, Hyung Geun; Kim, Haejung; Yoon, Sangsun; Hong, Seung Bok; Koo, Sun Hoe; Kim, Jimyung; Kim, Jongwan; Roh, Kyoung Ho

    2010-07-01

    Using an EZ-Step MRSA rapid kit, a novel screening test for methicillin-resistant Staphylococcus aureus (MRSA) that detects penicillin-binding protein 2a, 34 of 36 MRSA-positive clinical blood culture samples were positive on direct testing (sensitivity, 94.4%), whereas 21 of 21 methicillin-susceptible S. aureus-positive samples were negative (specificity, 100%).

  11. 3G Standards

    DEFF Research Database (Denmark)

    Saugstrup, Dan; Henten, Anders

    2006-01-01

    Purpose – The main purpose of this paper is to analyze which standard/technology will win the 3G mobile markets. In addition, two sub topics are examined. First, which kind of victory will it be – will one technological solution be all-dominating or is co-existence more likely? Second, which....... Originality/value – The paper is based on the understanding that a vast array of different factors in a complex dynamic environment goes into the determination of the outcome of such standardization games. However, the battle between 3G standards has already reached a level, where relatively certain...... predictions can be made. And, the paper contributes with a methodologically based discussion concerning the outcome of the battle between 3G standards....

  12. 5G. Trendthema 41

    OpenAIRE

    Tiemann, Jens

    2016-01-01

    Technikexperten und Politiker sprechen unter dem Schlagwort 5G von einer kommenden Mobilfunkgeneration, die die Digitalisierung der Gesellschaft auf eine neue Stufe heben wird. So soll 5G etwa Industrie-Roboter miteinander vernetzen und mobilen Anwendungen der erweiterten Realität zum Durchbruch verhelfen. Für solche Anwendungen braucht es hohe Bandbreiten, eine Übertragung in Echtzeit und die Vernetzung einer großen Anzahl an smarten Dingen - alles natürlich drahtlos und sicher. All dies sol...

  13. 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.

  14. FANTASTIC-5G

    DEFF Research Database (Denmark)

    Schaich, Frank; Sayrac, Berna; Elayoubi, Salaheddine

    2016-01-01

    -service support below 6 GHz will be too costly. FANTASTIC-5G will develop a new multi-service air interface through a modular design. To allow the system to adapt to the anticipated heterogeneity, some properties need to be pursued, like simplicity, flexibility, scalability, versatility, efficiency and future...

  15. G A Adebayo

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics. G A Adebayo. Articles written in Pramana – Journal of Physics. Volume 64 Issue 2 February 2005 pp 269-279 Research Articles. Structures and autocorrelation functions of liquid Al and Mg modelled via Lennard-Jones potential from molecular dynamics simulation.

  16. G P Kothiyal

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. G P Kothiyal. Articles written in Bulletin of Materials Science. Volume 23 Issue 5 October 2000 pp 377-382 Glass Ceramics. Preparation and characterization of magnesium–aluminium–silicate glass ceramics · Madhumita Goswami T Mirza A Sarkar Shobha Manikandan ...

  17. Does "g" Exist?

    Science.gov (United States)

    Detterman, Douglas K.

    1982-01-01

    In an argument for orthogonal variables to explain intelligence, higher-order constructs, including "g" as a single thing in intelligence, are suggested to inevitably result from complex systems with interrelated parts. Biological reductionism and other arguments for the higher-order constructs as explanations of intellectual functioning…

  18. G-matrices

    Czech Academy of Sciences Publication Activity Database

    Fiedler, Miroslav; Hall, F.J.

    2012-01-01

    Roč. 436, č. 3 (2012), s. 731-741 ISSN 0024-3795 Institutional research plan: CEZ:AV0Z10300504 Keywords : G-matrix * Cauchy matrix * sign pattern matrix * potentially orthogonal sign pattern Subject RIV: BA - General Mathematics Impact factor: 0.968, year: 2012

  19. 5G wireless technologies

    CERN Document Server

    Alexiou, Angeliki

    2017-01-01

    Mobile data traffic is expected to exceed traffic from wired devices in the next couple of years. This book presents a roadmap of 5G, from advanced radio technologies to innovative resource management approaches and novel network architectures and system concepts.

  20. L V G Rao

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Earth System Science. L V G Rao. Articles written in Journal of Earth System Science. Volume 109 Issue 2 June 2000 pp 255-265. Thermohaline structure and circulation in the upper layers of the southern Bay of Bengal during BOBMEX-Pilot (October — November 1998) · V Ramesh Babu V S N ...