21 CFR 211.176 - Penicillin contamination.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Penicillin contamination. 211.176 Section 211.176... Penicillin contamination. If a reasonable possibility exists that a non-penicillin drug product has been exposed to cross-contamination with penicillin, the non-penicillin drug product shall be tested for the...

21 CFR 211.176 - Penicillin contamination.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Penicillin contamination. 211.176 Section 211.176... Penicillin contamination. If a reasonable possibility exists that a non-penicillin drug product has been exposed to cross-contamination with penicillin, the non-penicillin drug product shall be tested for the...

21 CFR 558.460 - Penicillin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

21 CFR 558.460 - Penicillin.

Code of Federal Regulations, 2010 CFR

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...

21 CFR 558.460 - Penicillin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

21 CFR 558.460 - Penicillin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

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

PubMed

Ferech, Matus; Coenen, Samuel; Dvorakova, Katerina; Hendrickx, Erik; Suetens, Carl; Goossens, Herman

2006-08-01

Data on outpatient penicillin use in Europe were collected from 25 countries within the ESAC project, funded by DG SANCO of the European Commission, using the WHO ATC/DDD methodology. For the period 1997-2003, data on outpatient use of systemic penicillins aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2004) per 1000 inhabitants per day (DID). Of the 'Penicillins' (J01C), outpatient use of narrow-spectrum penicillins (J01CE), broad-spectrum penicillins (J01CA), penicillinase-resistant penicillins (J01CF) and combinations with beta-lactamase inhibitors (J01CR) in 25 European countries was analysed in detail. Total outpatient penicillin use in 2003 varied by a factor of 4 between the country with the highest (15.27 DID in Slovakia) and lowest use (3.86 DID in the Netherlands). Narrow-spectrum penicillins, broad-spectrum penicillins and combinations with beta-lactamase inhibitors were used most in 4, 12 and 9 countries, respectively. Penicillin use increased by more than 1 DID in nine countries, whereas it decreased by more than 1 DID in two countries (Czech Republic, France). An increase of the use of combinations with beta-lactamase inhibitors by more than 10% in 10 countries coincided with an equal decrease of broad-spectrum penicillins in seven countries and narrow-spectrum penicillins in three countries. Penicillins represent the most widely used antibiotic class in all 25 participating countries; albeit with considerable variation of their use patterns. A distinct shift from narrow-spectrum penicillins to broad-spectrum penicillins, and specifically their combinations with beta-lactamase inhibitors, was observed during the period 1997-2003.

Penicillin Dried Blood Spot Assay for Use in Patients Receiving Intramuscular Benzathine Penicillin G and Other Penicillin Preparations To Prevent Rheumatic Fever.

PubMed

Page-Sharp, Madhu; Coward, Jonathan; Moore, Brioni R; Salman, Sam; Marshall, Lewis; Davis, Timothy M E; Batty, Kevin T; Manning, Laurens

2017-08-01

Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a secondary prophylaxis to prevent recurrent episodes of acute rheumatic fever and subsequent RHD. Following intramuscular injection, BPG is hydrolyzed to penicillin G (benzylpenicillin). However, little is known of the pharmacokinetics (PK) of BPG in pediatric populations at high risk of RHD or of the pharmacokinetic-pharmacodynamic relationship between penicillin exposure and clinically relevant outcomes. Dried blood spot (DBS) assays can facilitate PK studies in situations where frequent venous blood sampling is logistically difficult. A liquid chromatography-mass spectroscopy assay for penicillin G in plasma and DBS was developed and validated. Application of the DBS assay for PK studies was confirmed using samples from adult patients receiving penicillin as part of an infection management plan. The limit of quantification for penicillin G in DBS was 0.005 mg/liter. Penicillin G is stable in DBS for approximately 12 h at room temperature (22°C), 6 days at 4°C, and >1 month at -20°C. Plasma and DBS penicillin G concentrations for patients receiving BPG and penicillin G given via bolus doses correlated well and had comparable time-concentration profiles. There was poor correlation for patients receiving penicillin via continuous infusions, perhaps as a result of the presence of residual penicillin in the peripherally inserted central catheter, from which the plasma samples were collected. The present DBS penicillin G assay can be used as a surrogate for plasma concentrations to provide valid PK data for studies of BPG and other penicillin preparations developed to prevent rheumatic fever and RHD. Copyright © 2017 American Society for Microbiology.

Skin testing and oral penicillin challenge in patients with a history of remote penicillin allergy.

PubMed

Goldberg, Arnon; Confino-Cohen, Ronit

2008-01-01

Penicillin administration is usually contraindicated in penicillin-allergic patients with positive skin test results. To examine whether penicillin oral challenge for patients with a history of remote non-life-threatening allergic reaction to penicillin can be well tolerated irrespective of skin test results. In a prospective open-label trial, 8,702 individuals were screened between November 1998 and January 2000. Of 687 patients with a non-life-threatening allergic reaction to penicillin, occurring longer than 3 years earlier, 169 were enrolled. Regardless of the response to penicillin skin testing, patients received the usual 1-day dosage of penicillin and amoxicillin, on 2 separate occasions. Two to 6 years later, a follow-up was conducted to assess the outcomes of further penicillin administration. A total of 272 combined skin tests and oral challenges were performed on 169 patients. Among 137 challenges with a positive skin test result and 135 patients with a negative skin test result, 9 (6.6%) and 5 (3.7%) (P = .29), respectively, developed a mild rash to oral challenge. At follow-up, 2 to 6 years afterward, 3 of 55 patients (5.5%) who were given a full treatment course of penicillin developed a mild skin eruption. Positive penicillin skin test results for patients with a remote history of non-life-threatening allergic reaction to penicillin were not associated with a greater prevalence of adverse reactions to oral challenge with penicillin than negative results. Because skin testing is considered the gold standard and the safest method for predicting tolerance to penicillin administration, oral penicillin challenge may be used as a diagnostic method only in these specific patients when skin testing is not feasible.

Penicillin Dried Blood Spot Assay for Use in Patients Receiving Intramuscular Benzathine Penicillin G and Other Penicillin Preparations To Prevent Rheumatic Fever

PubMed Central

Page-Sharp, Madhu; Coward, Jonathan; Moore, Brioni R.; Marshall, Lewis; Batty, Kevin T.

2017-01-01

ABSTRACT Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a secondary prophylaxis to prevent recurrent episodes of acute rheumatic fever and subsequent RHD. Following intramuscular injection, BPG is hydrolyzed to penicillin G (benzylpenicillin). However, little is known of the pharmacokinetics (PK) of BPG in pediatric populations at high risk of RHD or of the pharmacokinetic-pharmacodynamic relationship between penicillin exposure and clinically relevant outcomes. Dried blood spot (DBS) assays can facilitate PK studies in situations where frequent venous blood sampling is logistically difficult. A liquid chromatography-mass spectroscopy assay for penicillin G in plasma and DBS was developed and validated. Application of the DBS assay for PK studies was confirmed using samples from adult patients receiving penicillin as part of an infection management plan. The limit of quantification for penicillin G in DBS was 0.005 mg/liter. Penicillin G is stable in DBS for approximately 12 h at room temperature (22°C), 6 days at 4°C, and >1 month at −20°C. Plasma and DBS penicillin G concentrations for patients receiving BPG and penicillin G given via bolus doses correlated well and had comparable time-concentration profiles. There was poor correlation for patients receiving penicillin via continuous infusions, perhaps as a result of the presence of residual penicillin in the peripherally inserted central catheter, from which the plasma samples were collected. The present DBS penicillin G assay can be used as a surrogate for plasma concentrations to provide valid PK data for studies of BPG and other penicillin preparations developed to prevent rheumatic fever and RHD. PMID:28559267

Unusual effects of penicillin G and chloramphenicol on the growth of Moraxella osloensis.

PubMed

DeLeys, R J; Juni, E

1977-11-01

Growth of exponential-phase liquid cultures of Moraxella osloensis was inhibited by 0.5 U of penicillin G per ml. For this organism, low concentrations of penicillin acted primarily in a bacteriostatic rather than in a bactericidal manner. At higher concentrations of penicillin some killing did take place, but the rate of killing was rather slow and appeared to be independent of penicillin concentration. Microscopic observation of cells from penicillin-treated cultures showed little or no cellular swelling or lysis. The total cell count did not decrease significantly during 6 h of incubation in 5,000 U of penicillin per ml. The rates of respiration, nucleic acid synthesis, and protein synthesis were not affected by the presence of penicillin. Attempts to counteract the bactericidal action of high concentrations of penicillin with growth inhibitory concentrations of chloramphenicol were unsuccessful, since chloramphenicol itself was more bactericidal than penicillin for M. osloensis.

Unusual Effects of Penicillin G and Chloramphenicol on the Growth of Moraxella osloensis

PubMed Central

DeLeys, Robert J.; Juni, Elliot

1977-01-01

Growth of exponential-phase liquid cultures of Moraxella osloensis was inhibited by 0.5 U of penicillin G per ml. For this organism, low concentrations of penicillin acted primarily in a bacteriostatic rather than in a bactericidal manner. At higher concentrations of penicillin some killing did take place, but the rate of killing was rather slow and appeared to be independent of penicillin concentration. Microscopic observation of cells from penicillin-treated cultures showed little or no cellular swelling or lysis. The total cell count did not decrease significantly during 6 h of incubation in 5,000 U of penicillin per ml. The rates of respiration, nucleic acid synthesis, and protein synthesis were not affected by the presence of penicillin. Attempts to counteract the bactericidal action of high concentrations of penicillin with growth inhibitory concentrations of chloramphenicol were unsuccessful, since chloramphenicol itself was more bactericidal than penicillin for M. osloensis. PMID:335964

Association between chronic urticaria and self-reported penicillin allergy.

PubMed

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.

Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions.

PubMed

Han, Jiayin; Yi, Yan; Li, Chunying; Zhang, Yushi; Wang, Lianmei; Zhao, Yong; Pan, Chen; Liang, Aihua

2016-09-13

The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions.

Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions

PubMed Central

Han, Jiayin; Yi, Yan; Li, Chunying; Zhang, Yushi; Wang, Lianmei; Zhao, Yong; Pan, Chen; Liang, Aihua

2016-01-01

The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions. PMID:27619816

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

PubMed

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.

Elective penicillin skin testing in a pediatric outpatient setting.

PubMed

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.

Long-Term Follow-Up After Penicillin Allergy Delabeling in Ambulatory Patients.

PubMed

Lachover-Roth, Idit; Sharon, Shoshan; Rosman, Yossi; Meir-Shafrir, Keren; Confino-Cohen, Ronit

2018-05-22

Unverified penicillin allergy label has negative health implications. To address this, several delabeling methods have been proposed. To appraise the long-term outcomes of the penicillin allergy evaluation in ambulatory patients, focusing on subsequent use of penicillins in individuals found not allergic. A secondary objective was to examine the consistency between the evaluation's recommendations and the allergy label. A retrospective medical records review and phone survey were carried out in ambulatory patients who were evaluated for suspected penicillin allergy in our allergy unit. Patients with an uneventful oral challenge test (OCT) were interviewed regarding subsequent use of penicillins. Medical records were examined for antibiotic prescriptions and purchases. The records were also investigated for existing/erased penicillin allergy label and its consistency with the allergy evaluation. Six hundred thirty-nine patients with an uneventful OCT were available for the survey. During a 56-month follow-up, 70% (447 patients) had used penicillins at least once. One hundred ninety-two patients (30%) did not use penicillins. The main reason for not using penicillins was lack of a clinical indication. Three hundred thirty-five patients (51.22%) carried a penicillin allergy label in their electronic medical file in spite of an uneventful OCT. Penicillin allergy annulling via OCT has proven to be effective. Most of the patients who previously avoided penicillins have reused penicillins safely. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

21 CFR 558.274 - Hygromycin B.

Code of Federal Regulations, 2011 CFR

2011-04-01

... methylene disalicylate or zinc bacitracin; withdraw 3 days before slaughter Bacitracin plus penicillin (100...% of penicillin plus not less than 50% of bacitracin; as procaine penicillin plus bacitracin methylene... penicillin; as procaine penicillin plus zinc bacitracin; withdraw 3 days before slaughter 3. Chickens...

21 CFR 558.274 - Hygromycin B.

Code of Federal Regulations, 2010 CFR

2010-04-01

... methylene disalicylate or zinc bacitracin; withdraw 3 days before slaughter Bacitracin plus penicillin (100...% of penicillin plus not less than 50% of bacitracin; as procaine penicillin plus bacitracin methylene... penicillin; as procaine penicillin plus zinc bacitracin; withdraw 3 days before slaughter 3. Chickens...

A retrospective comparison of false negative skin test rates in penicillin allergy, using pencilloyl-poly-lysine and minor determinants or Penicillin G, followed by open challenge.

PubMed

Rosenfield, Lana; Kalicinsky, Chrystyna; Warrington, Richard

2015-01-01

A history of penicillin allergy in patients is common, but only 10-15 % are truly allergic. While the gold standard for diagnosing penicillin allergy is challenge, it is not recommended that this be done without first carrying out diagnostic skin testing. This is carried out with the major determinant benzylpenicilloyl (PPL) and the minor determinant mixture (MDM), consisting of penilloate, penicilloate and Penicillin G. However, since availability of the MDM is limited, Penicillin G alone has been used. A retrospective chart review was carried out on patients tested for penicillin allergy in the Clinical Immunology and Allergy Clinic at the Health Sciences Centre, Winnipeg, Canada between 2005 and 2013. A total of 521 patients charts were reviewed, of whom 240 had skin testing, ImmunoCap(®) for IgE to Penicillin G and V and had oral challenges with penicillin, amoxicillin or cloxacillin. 17/240 (7.5 %) were skin test positive, 8 to PPL, 4 to MDM and 5 to Penicillin G. One was also positive on ImmunoCap(®) testing. Three patients had negative skin tests but weakly positive ImmunoCap(®). 222 patients with negative skin tests and serological tests were challenged. Of these, 12 patients reacted to challenge. Three of the challenges were equivocal. Of the nine patients with definite positive challenges, three were tested with Penicillin G and six with MDM. Therefore the false negative rates for testing were 2.3 % with PPL and Penicillin G and 6.97 % for PPL and MDM. The difference was not significant (p = 0.0856). In this group of patients with a history of penicillin allergy tested with the major determinant of benzyl penicillin and either MDM or Penicillin G, there was no difference in the rate of false negative testing, based on oral penicillin challenges. Therefore, Penicillin G can be safely used as an alternative to MDM in diagnosing penicillin allergy.

Formation of 6-Aminopenicillanic Acid, Penicillins, and Penicillin Acylase by Various Fungi

PubMed Central

Cole, M.

1966-01-01

Several penicillin-producing fungi were examined for ability to produce 6-aminopenicillanic acid (6-APA) and penicillin acylase. 6-APA was found in corn steep liquor fermentations of Trichophyton mentagrophytes, Aspergillus ochraceous, and three strains of Penicillium sp. 6-APA was not detected in fermentations of Epidermophyton floccosum although penicillins were produced. 6-APA formed a large part of the total antibiotic production of T. mentagrophytes. The types of penicillins produced by various fungi were identified by paper chromatography, and it was found that all cultures produced benzylpenicillin. T. mentagrophytes and A. ochraceous showed increased yields of benzylpenicillin and the formation of phenoxymethylpenicillin in response to the addition to the fermentation medium of phenylacetic acid and phenoxyacetic acid, respectively. Washed mycelia of the three Penicillium spp. and two high penicillin-yielding strains of P. chrysogenum possessed penicillin acylase activity against phenoxymethylpenicillin. A. ochraceous, T. mentagrophytes, E. floccosum, and Cephalosporium sp. also had penicillin acylase activity against phenoxymethylpenicillin. Only two of the above fungi, T. mentagrophytes and E. floccosum, showed significant penicillin acylase activity against benzylpenicillin; in both cases it was very low. The acylase activity of A. ochraceous was considerably increased by culturing in the presence of phenoxyacetic acid. It is concluded that 6-APA frequently but not invariably accompanies the formation of penicillin, and that penicillin acylase activity against phenoxymethylpenicillin is present in all penicillin-producing fungi. PMID:5950252

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

PubMed

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.

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

PubMed

Macy, Eric

2015-08-01

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

21 CFR 522.1696b - Penicillin G procaine aqueous suspension.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 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...

21 CFR 522.1696b - Penicillin G procaine aqueous suspension.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

21 CFR 522.1696b - Penicillin G procaine aqueous suspension.

Code of Federal Regulations, 2010 CFR

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...

21 CFR 522.1696b - Penicillin G procaine aqueous suspension.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

21 CFR 522.1696b - Penicillin G procaine aqueous suspension.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

Metabolism of Penicillins to Penicilloic Acids and 6-Aminopenicillanic Acid in Man and Its Significance in Assessing Penicillin Absorption

PubMed Central

Cole, M.; Kenig, M. D.; Hewitt, Valerie A.

1973-01-01

Penicillins can be metabolized to penicilloic acids in man, the extent being dependent on the penicillin structure. In the phenoxy penicillin series, phenoxymethyl penicillin was found to be particularly unstable, but the higher homologues were more stable. In the isoxazolyl series, oxacillin was unstable, and progressive insertion of halogen in the phenyl ring increased stability. Ampicillin and amoxycillin showed some instability, ampicillin possibly being the more stable. After intramuscular administration, carbenicillin was very stable in the body, ampicillin was fairly stable, and benzyl penicillin was unstable. It is important to take into account the penicilloic acid content of urine when estimating total absorption of a penicillin. Increased stability in the body as well as slower renal clearance can lead to high concentrations in the serum. Penicilloic acids seemed to be more slowly cleared from the body than penicillins. The liver is probably the site of inactivation. PMID:4364176

Comparison of susceptibility test methods to detect penicillin susceptibility in Streptococcus pneumoniae isolates.

PubMed

Mohd Nasir, Mohd Desa; Parasakthi, Navaratnam

2004-06-01

The increasing prevalence of penicillin-resistant Streptococuus pneumoniae urges for fast and accurate susceptibility testing methods. This study evaluated the comparability of three commonly used techniques; disk diffusion, E-test and agar dilution, to detect penicillin susceptibility in clinical isolates of S. pneumoniae. Fifty pneumococcal isolates, obtained from patients at the University of Malaya Medical Centre, were selected to include both penicillin-susceptible strains and those that had decreased susceptibility (resistant and intermediate) to penicillin. The minimum inhibitory concentration (MIC) values of penicillin to serve as the reference was determined by the agar dilution method in which, based on the MIC breakpoints recommended by the National Committee for Clinical Laboratory Standards (NCCLS), 27 strains had decreased susceptibility to penicillin with 17 strains resistant and 10 intermediate. Comparing to the agar dilution method, oxacillin disk diffusion test detected all strains with decreased penicillin susceptibility as such while E-test showed a close agreement of susceptibility (92%) of the isolates to penicillin. This confirmed that oxacillin is a good screening test for S. pneumoniae isolates with decreased susceptibility to penicillin while E-test is very reliable for rapid and accurate detection of penicillin susceptibility.

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

PubMed

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.

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

PubMed Central

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

2016-01-01

Background 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. Objective To assess exposure to penicillin dust, penicillin active materials, and to report the frequency of penicillin resistance among pharmaceutical workers in Tehran, Iran. Methods 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. Results The mean overall concentrations of penicillin dust and penicillin active material were 6.6 and 4.3 mg/m3, 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). Conclusions 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. PMID:27388022

Experimental Streptococcus pneumoniae infection in mice for studying correlation of in vitro and in vivo activities of penicillin against pneumococci with various susceptibilities to penicillin.

PubMed Central

Knudsen, J D; Frimodt-Møller, N; Espersen, F

1995-01-01

The purpose of the study was to investigate the correlation of in vitro activity with the in vivo effect and the pharmacokinetics of penicillin in the treatment of infections with pneumococci with various susceptibilities to penicillin. We used 10 pneumococcal strains for which penicillin MICs ranged from 0.016 to 8 micrograms/ml. Time-kill curve experiments were performed with all strains. We found that the effect of penicillin in vitro is concentration independent, with a maximum effect at two to four times the MIC for penicillin-susceptible as well as penicillin-resistant pneumococci. The mouse peritonitis model with an inoculum of approximately 10(6) CFU, to which mucin was added, resulted in a reproducible lethal infection with the pneumococci. The 50% effective dose was determined for each strain, and we found a highly significant correlation between the log MIC and the log 50% effective dose of penicillin against these strains (P < 0.01). Furthermore, it was shown that the most important pharmacokinetic parameter determining the effect of penicillin in vivo was the time that the concentration of penicillin in serum was greater than the MIC. PMID:7574511

Penicillin and beta-lactam allergy: epidemiology and diagnosis.

PubMed

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.

Clinical history as a predictor of penicillin skin test outcome.

PubMed

Wong, Benjamin B L; Keith, Paul K; Waserman, Susan

2006-08-01

Up to 10% of the population reports an "allergy" to penicillin, whereas approximately 1.1% has positive penicillin skin test results. Where penicillin skin tests are unavailable, some have advocated using history to decide whether to use a penicillin-related antibiotic. To determine if clinical history predicts penicillin skin test results. Retrospective medical record review of 94 consecutive patients who had previously taken penicillin referred for penicillin allergy. Case histories were taken, penicillin skin tests performed, and an oral challenge recommended if skin test results were negative. Of 91 cases studied, the average patient age was 27 years (range, 6 months to 82 years; 36% female). Fifty-two (57%) experienced hives as their main adverse reaction. Sixteen (18%) had at least 1 positive test result. Of this group, 9 had hives as their main symptom, whereas 1 had respiratory problems and 1 had angioedema. Most patients with positive skin test results had experienced their reaction at least 3 years ago. Regression analysis showed that age, sex, and clinical history, including type of reaction, time of reaction after penicillin ingestion, or time since the last reaction, were not associated with skin test positivity. Seventy-two (96%) of the 75 patients who had negative skin test results underwent oral challenge. Seventy had negative challenge results. The negative predictive value of a negative penicillin skin test result was 97%. Clinical history was not predictive of subsequent penicillin skin test results.

21 CFR 520.1696d - Penicillin V potassium tablets.

Code of Federal Regulations, 2010 CFR

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...

21 CFR 556.510 - Penicillin.

Code of Federal Regulations, 2010 CFR

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...

21 CFR 556.510 - Penicillin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

21 CFR 520.1696d - Penicillin V potassium tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

21 CFR 520.1696d - Penicillin V potassium tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

21 CFR 556.510 - Penicillin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

21 CFR 556.510 - Penicillin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

21 CFR 556.510 - Penicillin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 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...

SYNTHESIS OF PENICILLINS FOR TRACER STUDIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nettleton, D.E. Jr.; Johnson, D.L.; O'Herron, F.A.

1962-05-01

The synthesis of Penicillin K, Penicillin X, Penicillin F and its dihydro derivative, and C/sup 14/-labeled benzylpenicillin are described, starting from preparations containing 6aminopenlcillanic acid. (T.F.H.)

Safety of meropenem in patients reporting penicillin allergy: lack of allergic cross reactions.

PubMed

Cunha, B A; Hamid, N S; Krol, V; Eisenstein, L

2008-04-01

Over the years, meropenem has become the mainstay of empiric therapy for serious systemic infections in critically ill patients. Although we have had extensive clinical experience since 1996 using meropenem safely in treating hundreds of patients with reported allergic reactions to penicillin without any adverse events, we have not published our experience. This study was conducted to document our clinical practice experience. Accordingly, over a 12-month period we prospectively monitored 110 patients treated with meropenem reporting penicillin allergic reactions for that 12-month period. Since early empiric therapy in such patients is essential, there is often no time for penicillin skin testing. Penicillin skin testing was not done in this "real world" clinical study. Patients were divided into two groups, depending on the nature of their penicillin allergic reactions. During a 12-month period, 110 patients with non-anaphylactic (59) and anaphylactic (51) penicillin allergic reactions tolerated prolonged meropenem therapy (1-4 weeks) safely without any allergic reactions. Based on these data and our previous clinical experience, there appears to be little/no potential cross reactivity between meropenem and penicillins even in patients with a definite history of anaphylactic reactions to penicillins. To the best of our knowledge, this is the first prospective clinical study demonstrating that meropenem may be safely given to patients with known/unknown allergic reactions to penicillin, including those with anaphylactic reactions, without penicillin skin testing. We conclude that meropenem may be given safely to patients reporting a history of non-anaphylactic or anaphylactic allergic reactions to penicillins without penicillin skin testing.

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

PubMed

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 < .0001). In superficial wound cultures, 21% were 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.

Tackling inpatient penicillin allergies: Assessing tools for antimicrobial stewardship.

PubMed

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.

US antibiotic stewardship and penicillin allergy.

PubMed

Wada, Kara J; Calhoun, Karen H

2017-06-01

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

Penicillin G Benzathine Injection

MedlinePlus

... to treat and prevent certain infections caused by bacteria. Penicillin G benzathine injection is in a class of antibiotics called penicillins. It works by killing bacteria that cause infections.Antibiotics such as penicillin G ...

Penicillin G (Potassium, Sodium) Injection

MedlinePlus

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. ...

Penicillin biosynthesis in Aspergillus oryzae and its overproduction by genetic engineering.

PubMed

Marui, Junichiro; Ohashi-Kunihiro, Sumiko; Ando, Tomohiro; Nishimura, Marie; Koike, Hideaki; Machida, Masayuki

2010-07-01

Aspergillus oryzae penicillin biosynthetic genes were clustered. The penicillin production was positively regulated by VeA, a global gene regulator required for transcriptional expression of the penicillin biosynthetic genes. Overexpression of the biosynthetic genes by a strong promoter yielded a greater than 100-fold increase in penicillin production. 2010 Elsevier B.V. All rights reserved.

21 CFR 526.1696b - Penicillin G procaine-dihydrostreptomycin in soybean oil for intramammary infusion (dry cows).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin G procaine-dihydrostreptomycin in... INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696b Penicillin G procaine-dihydrostreptomycin in soybean oil... penicillin G procaine equivalent to 200,000 units of penicillin G and dihydrostreptomycin sulfate equivalent...

21 CFR 526.1696b - Penicillin G procaine-dihydrostreptomycin in soybean oil for intramammary infusion (dry cows).

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin G procaine-dihydrostreptomycin in... INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696b Penicillin G procaine-dihydrostreptomycin in soybean oil... penicillin G procaine equivalent to 200,000 units of penicillin G and dihydrostreptomycin sulfate equivalent...

21 CFR 558.366 - Nicarbazin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... roxarsone by No. 046573 in § 510.600(c) of this chapter 066104 Penicillin 2.4 to 50 Broiler chickens: As an... tissue. Penicillin as procaine penicillin G. Nicarbazin and penicillin as provided by No. 066104 in § 510.600(c) of this chapter 066104 Penicillin 2.4 to 50 and roxarsone 22.7 to 45.4 Broiler chickens: As an...

21 CFR 526.1696b - Penicillin G procaine-dihydrostreptomycin in soybean oil for intramammary infusion (dry cows).

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin G procaine-dihydrostreptomycin in... INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696b Penicillin G procaine-dihydrostreptomycin in soybean oil... penicillin G procaine equivalent to 200,000 units of penicillin G and dihydrostreptomycin sulfate equivalent...

21 CFR 526.1696b - Penicillin G procaine-dihydrostreptomycin in soybean oil for intramammary infusion (dry cows).

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin G procaine-dihydrostreptomycin in... INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696b Penicillin G procaine-dihydrostreptomycin in soybean oil... penicillin G procaine equivalent to 200,000 units of penicillin G and dihydrostreptomycin sulfate equivalent...

21 CFR 558.366 - Nicarbazin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... roxarsone by No. 046573 in § 510.600(c) of this chapter 066104 Penicillin 2.4 to 50 Broiler chickens: As an... tissue. Penicillin as procaine penicillin G. Nicarbazin and penicillin as provided by No. 066104 in § 510.600(c) of this chapter 066104 Penicillin 2.4 to 50 and roxarsone 22.7 to 45.4 Broiler chickens: As an...

21 CFR 558.366 - Nicarbazin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... below 113.5 g/ton. Withdraw 5 days before slaughter for use levels above 113.5 g/ton. 066104 Penicillin... elimination of the drug from edible tissue. Penicillin as procaine penicillin G. Nicarbazin and penicillin as provided by No. 066104 in § 510.600(c) of this chapter. 066104 Penicillin 2.4 to 50 and roxarsone 22.7 to...

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

PubMed

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.

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

PubMed

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.

Affinities of penicillins and cephalosporins for the penicillin-binding proteins of Escherichia coli K-12 and their antibacterial activity.

PubMed Central

Curtis, N A; Orr, D; Ross, G W; Boulton, M G

1979-01-01

The affinities of a range of penicillins and cephalosporins for ther penicillin-binding proteins of Escherichia coli K-12 have been studied, and the results were compared with the antibacterial activity of the compounds against E. coli K-12 and an isogenic permeability mutant. Different penicillins and cephalosporins exhibited different affinities for the "essential" penicillin-binding proteins of E. coli K-12, in a manner which directly correlated with their observed effects upon bacterial morphology. Furthermore, the affinities of the compounds for their "primary" lethal penicillin-binding protein targets showed close agreement with their antibacterial activities against the permeability mutant. Images PMID:393164

21 CFR 522.1696c - Penicillin G procaine in oil.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

21 CFR 522.1696c - Penicillin G procaine in oil.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 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. 054771 in § 510.600(c) of this...

21 CFR 522.1696c - Penicillin G procaine in oil.

Code of Federal Regulations, 2010 CFR

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...

21 CFR 522.1696c - Penicillin G procaine in oil.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

21 CFR 522.1696c - Penicillin G procaine in oil.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

In Vitro Activity of p-Hydroxybenzyl Penicillin (Penicillin X) and Five Other Penicillins Against Neisseria gonorrhoeae: Comparisons of Strains from Patients with Uncomplicated Infections and from Women with Pelvic Inflammatory Disease

PubMed Central

Sackel, Stephen G.; Alpert, Susan; Rosner, Bernard; McCormack, William M.; Finland, Maxwell

1977-01-01

Minimum inhibitory concentrations (MICs) of six penicillins against 95 strains of Neisseria gonorrhoeae from patients with uncomplicated anogenital infections and 22 strains from women with pelvic inflammatory disease were determined by an agar plate dilution method, using an inocula replicator. Against all 117 strains, the order of activity observed was: BL-P1654 > penicillin X > penicillin G > ampicillin > amoxicillin = carbenicillin. MICs against strains isolated from women with gonococcal pelvic inflammatory disease were significantly higher than those against isolates from uncomplicated infections: BL-P1654, P < 0.001; penicillin X, P < 0.001; penicillin G, P < 0.001; ampicillin, P < 0.001; and amoxicillin, P < 0.05. MICs of penicillin G were ≥0.125 μg/ml against 33 (36%) of the 92 strains from patients with uncomplicated infections, as contrasted with 15 (68%) of the 22 isolates from women with pelvic inflammatory disease (P < 0.01). The means of the MICs of penicillin G were 0.06 μg/ml for the former and 0.14 μg/ml for the latter. PMID:407840

Skin testing only with penicillin G in children with a history of penicillin allergy.

PubMed

Picard, Matthieu; Paradis, Louis; Bégin, Philippe; Paradis, Jean; Des Roches, Anne

2014-07-01

The absence of commercially available penicilloyl-polylysine (PPL) for most of the last decade severely hampered the practice of penicillin allergy evaluation because skin testing without PPL is reported to have a poor negative predictive value (NPV). To determine the safety and NPV of skin testing without PPL using only penicillin G followed by a 3-dose graded challenge to the incriminated penicillin in children with a history of penicillin allergy. Patients evaluated for a history of penicillin allergy at the CHU Sainte-Justine Allergy Clinic between December 2006 and December 2009 were skin tested only with penicillin G and underwent a 3-dose graded challenge to the culprit penicillin if the skin test result was negative. Among 563 patients skin tested to penicillin G, 185 (33%) had a positive skin test result. These patients had a shorter interval between the initial reaction and skin testing compared with patients with a negative skin test result (P = .03). A total of 375 of 378 patients (99%) with a negative skin test result were challenged and 18 (4.8%) reacted, translating into a NPV of 95.2% (95% confidence interval [CI], 92.5%-97.1%). Three of 17 patients with a history of anaphylaxis and a negative skin test result reacted to challenge (NPV, 82.4%; 95% CI, 59.0-93.8%). All challenge reactions were mild and resolved promptly with treatment. Among children with a history of penicillin allergy, skin testing only with penicillin G followed by a 3-dose graded challenge to the incriminated penicillin is safe and yields a good NPV. This approach could be useful when PPL is unavailable. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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 <0.001). During the study period, 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.

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

PubMed

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], P<.01). An increased prescription of penicillin (range 9.9%-49%) and cephalosporin (range 10.7%-48%) antibiotics was reported. Vancomycin and fluoroquinolone use was decreased. Inpatient penicillin allergy 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.

Penicillin G Procaine Injection

MedlinePlus

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 ...

Hitler's penicillin.

PubMed

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.

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

PubMed

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 biosynthesis and secretion of penicillin. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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.

Morbidity in Pregnant Women Associated with Unverified Penicillin Allergies, Antibiotic Use, and Group B Streptococcus Infections.

PubMed

Desai, Shilpa H; Kaplan, Michael S; Chen, Qiaoling; Macy, Eric M

2017-01-01

The morbidity potentially associated with unverified penicillin allergy in pregnant women, with and without group B streptococcus (GBS) infections, is unknown. Penicillin allergy testing is safe during pregnancy but is done infrequently. To determine morbidity associated with antibiotic use in a large cohort of pregnant women, with and without an unverified history of penicillin allergy, and with and without GBS. Retrospective. All pregnant women who delivered live infants in Kaiser Permanente Southern California between January 1, 2009, and December 31, 2014, were identified. Penicillin allergy status at delivery, delivery method, maternal and infant hospital utilization, peripartum antibiotic exposures, new antibiotic-associated adverse drug reactions, and new Clostridium difficile infections. There were 170,379 unique women who had 201,316 pregnancies during the study period. There were 16,084 pregnancies in women with an active, but unverified, penicillin allergy at delivery. There were 42,524 pregnancies in GBS-positive women, and 3500 also had a penicillin allergy. Women with a penicillin allergy, with or without GBS, had significantly (about 10%) higher cesarean section rates and spent significantly more (about 0.1) days in the hospital after delivery. Among GBS-positive women, those with an unverified penicillin allergy were exposed to significantly more cefazolin, clindamycin, vancomycin, and gentamicin and had significantly higher rates of adverse drug reactions associated with all antibiotic use. Unverified penicillin allergy is associated with more hospital utilization and additional morbidity. Penicillin allergy testing of pregnant women with a history of penicillin allergy may help reduce these unwanted outcomes.

Penicillin-binding protein 1A, 2B, and 2X alterations in Canadian isolates of penicillin-resistant Streptococcus pneumoniae.

PubMed

Nichol, Kimberly A; Zhanel, George G; Hoban, Daryl J

2002-10-01

Alterations within the penicillin-binding domain of penicillin-binding protein (PBP) genes pbp1a, pbp2b, and pbp2x were determined for 15 Canadian isolates of Streptococcus pneumoniae. All penicillin-nonsusceptible S. pneumoniae isolates showed a variety of PBP 2X substitutions and contained a Thr445-Ala change after the PBP 2B SSN motif. Only isolates for which penicillin MICs were > or =0.5 micro g/ml had PBP 1A alterations near the STMK and SRN motifs. Sequence analysis revealed identical PBP 1A, PBP 2B, and PBP 2X substitution patterns among all isolates for which penicillin MICs were > or =1 micro g/ml.

Penicillin-Binding Protein 1A, 2B, and 2X Alterations in Canadian Isolates of Penicillin-Resistant Streptococcus pneumoniae

PubMed Central

Nichol, Kimberly A.; Zhanel, George G.; Hoban, Daryl J.

2002-01-01

Alterations within the penicillin-binding domain of penicillin-binding protein (PBP) genes pbp1a, pbp2b, and pbp2x were determined for 15 Canadian isolates of Streptococcus pneumoniae. All penicillin-nonsusceptible S. pneumoniae isolates showed a variety of PBP 2X substitutions and contained a Thr445-Ala change after the PBP 2B SSN motif. Only isolates for which penicillin MICs were ≥0.5 μg/ml had PBP 1A alterations near the STMK and SRN motifs. Sequence analysis revealed identical PBP 1A, PBP 2B, and PBP 2X substitution patterns among all isolates for which penicillin MICs were ≥1 μg/ml. PMID:12234855

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

PubMed

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 < 0.01). In urticaria group, the positive rate of specific-cephalosporin IgE was significantly higher than in other symptoms group (30.65% vs. 8.11%, p < 0.05). The analysis of drugs which have the same or similar side-chains showed that benzylpenicillanyl-IgE (BPA-IgE), ampicillanyl-IgE (APA-IgE), amoxicillanyl-IgE (AXA-IgE) were respectively related to cephalothanyl-IgE (CLA-IgE), cephalexanyl-IgE (CEXA-IgE), cephalexanyl-IgE (CEXA-IgE)in sera of 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 < 0.01). Radioallergosorbent test and radioallergosorbent inhibition test confirmed that both nuclear structure and R1 side-chain contribute to IgE recognition. There exists cross-reactivity between cephalosporins and 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.

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

PubMed

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.

Improved fiber-optic chemical sensor for penicillin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Healy, B.G.; Walt, D.R.

An optical penicillin biosensor is described, based on the enzyme penicillinase. The sensor is fabricated by selective photodeposition of analyte-sensitive polymer matrices on optical imaging fibers. The penicillin-sensitive matrices are fabricated by immobilizing the enzyme as micrometer-sized particles in a polymer hydrogel with a covalently bound pH indicator. An array of penicillin-sensitive and pH-sensitive matrices are fabricated on the same fiber. This array allows for the simultaneous, independent measurement of pH and penicillin. Independent measurement of the two analytes allows penicillin to be quantitated in the presence of a concurrent pH change. An analysis was conducted of enzyme kinetic parametersmore » in order to model the penicillin response of the sensor at all pH values. This analysis accounts for the varying activity of the immobilized penicillinase at different pH values. The sensor detects penicillin in the range 0.25-10.0 mM in the pH range 6.2-7.5. The sensor was used to quantify penicillin concentration produced during a Penicillium chrysogenum fermentation. 27 refs., 7 figs., 1 tab.« less

Clinical and Microbiological Aspects of β-Lactam Resistance in Staphylococcus lugdunensis

PubMed Central

McHardy, Ian H.; Veltman, Jennifer; Hindler, Janet; Bruxvoort, Katia; Carvalho, Marissa M.

2016-01-01

ABSTRACT Antimicrobial susceptibility results from broth microdilution MIC testing of 993 Staphylococcus lugdunensis isolates recovered from patients at a tertiary care medical center from 2008 to 2015 were reviewed. Ninety-two oxacillin-susceptible isolates were selected to assess the accuracy of penicillin MIC testing, the penicillin disk diffusion test, and three β-lactamase tests, including the cefoxitin-induced nitrocefin test, penicillin cloverleaf assay, and penicillin disk zone edge test. The results of all phenotypic tests were compared to the results of blaZ PCR. The medical records of 62 patients from whom S. lugdunensis was isolated, including 31 penicillin-susceptible and 31 penicillin-resistant strains, were retrospectively reviewed to evaluate the clinical significance of S. lugdunensis isolation, the antimicrobial agents prescribed, if any, and the clinical outcome. MIC testing revealed that 517/993 (52.1%) isolates were susceptible to penicillin and 946/993 (95.3%) were susceptible to oxacillin. The induced nitrocefin test was 100% sensitive and specific for the detection of β-lactamase compared to the blaZ PCR results, whereas the penicillin disk zone edge and cloverleaf tests showed sensitivities of 100% but specificities of only 9.1% and 89.1%, respectively. The penicillin MIC test had 100% categorical agreement with blaZ PCR, while penicillin disk diffusion yielded one major error. Only 3/31 patients with penicillin-susceptible isolates were treated with a penicillin family antimicrobial. The majority of cases were treated with other β-lactams, trimethoprim-sulfamethoxazole, or vancomycin. These data indicate that nearly all isolates of S. lugdunensis are susceptible to narrow-spectrum antimicrobial agents. Clinical laboratories in areas with resistance levels similar to those described here can help promote the use of these agents versus vancomycin by effectively designing their antimicrobial susceptibility reports to convey this message. PMID:27927926

Clinical and Microbiological Aspects of β-Lactam Resistance in Staphylococcus lugdunensis.

PubMed

McHardy, Ian H; Veltman, Jennifer; Hindler, Janet; Bruxvoort, Katia; Carvalho, Marissa M; Humphries, Romney M

2017-02-01

Antimicrobial susceptibility results from broth microdilution MIC testing of 993 Staphylococcus lugdunensis isolates recovered from patients at a tertiary care medical center from 2008 to 2015 were reviewed. Ninety-two oxacillin-susceptible isolates were selected to assess the accuracy of penicillin MIC testing, the penicillin disk diffusion test, and three β-lactamase tests, including the cefoxitin-induced nitrocefin test, penicillin cloverleaf assay, and penicillin disk zone edge test. The results of all phenotypic tests were compared to the results of blaZ PCR. The medical records of 62 patients from whom S. lugdunensis was isolated, including 31 penicillin-susceptible and 31 penicillin-resistant strains, were retrospectively reviewed to evaluate the clinical significance of S. lugdunensis isolation, the antimicrobial agents prescribed, if any, and the clinical outcome. MIC testing revealed that 517/993 (52.1%) isolates were susceptible to penicillin and 946/993 (95.3%) were susceptible to oxacillin. The induced nitrocefin test was 100% sensitive and specific for the detection of β-lactamase compared to the blaZ PCR results, whereas the penicillin disk zone edge and cloverleaf tests showed sensitivities of 100% but specificities of only 9.1% and 89.1%, respectively. The penicillin MIC test had 100% categorical agreement with blaZ PCR, while penicillin disk diffusion yielded one major error. Only 3/31 patients with penicillin-susceptible isolates were treated with a penicillin family antimicrobial. The majority of cases were treated with other β-lactams, trimethoprim-sulfamethoxazole, or vancomycin. These data indicate that nearly all isolates of S. lugdunensis are susceptible to narrow-spectrum antimicrobial agents. Clinical laboratories in areas with resistance levels similar to those described here can help promote the use of these agents versus vancomycin by effectively designing their antimicrobial susceptibility reports to convey this message. Copyright © 2017 American Society for Microbiology.

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

PubMed

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.

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

PubMed

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.

THE THERAPEUTIC ACTIVITY OF PENICILLINS F, G, K, AND X IN EXPERIMENTAL INFECTIONS WITH PNEUMOCOCCUS TYPE I AND STREPTOCOCCUS PYOGENES

PubMed Central

Eagle, Harry

1947-01-01

1. The relative bactericidal activities of penicillins F, G, K, and X against Type I pneumococcus in vitro were 60, 100, 180, and 135. The corresponding activities against Streptococcus pyogenes, strain C-203, were 75, 100, 115, and 145, respectively. 2. The total curative doses (CD50) of penicillins F, G, K, and X in pneumococcal infections of white mice (ten injections at 3 hour intervals) were 4.6, 3.8, 20, and 2.4 mg. per kg., respectively, or relative activities of 83, 100, 19, and 160, referred to G as 100. 3. The corresponding curative doses in streptococcal infections of white mice were 2.6, 1.3, 14.0, and 0.5 mg. per kg., or relative activities of 50, 100, 9, and 260. 4. Penicillin K was therefore one-tenth as active in vivo as would be implied by its bactericidal activity in vitro. This probably reflects its rapid inactivation in vivo, evidenced by the low and evanescent blood levels observed in both rabbits and man, and the low urinary recovery of this species of penicillin. 5. Penicillin X was significantly more active therapeutically than its bactericidal activity in vitro would imply. This probably reflects its slower inactivation in vivo, evidenced by the somewhat higher and more prolonged blood levels afforded by this penicillin in comparison with penicillin G. Judged by the mouse infections with the strains here used, penicillin X is the penicillin of choice in the treatment of infections with pneumococcus Type I and hemolytic streptococci. 6. The curative dose of penicillin in streptococcal and pneumococcal infections paralleled the varying susceptibility of these organisms to penicillin in vitro. PMID:19871606

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

PubMed

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.

Sub-inhibitory concentrations of penicillin G induce biofilm formation by field isolates of Actinobacillus pleuropneumoniae.

PubMed

Hathroubi, S; Fontaine-Gosselin, S-È; Tremblay, Y D N; Labrie, J; Jacques, M

2015-09-30

Actinobacillus pleuropneumoniae is a Gram-negative bacterium and causative agent of porcine pleuropneumonia. This is a highly contagious disease that causes important economic losses to the swine industry worldwide. Penicillins are extensively used in swine production and these antibiotics are associated with high systemic clearance and low oral bioavailability. This may expose A. pleuropneumoniae to sub-inhibitory concentrations of penicillin G when the antibiotic is administered orally. Our goal was to evaluate the effect of sub-minimum inhibitory concentration (MIC) of penicillin G on the biofilm formation of A. pleuropneumoniae. Biofilm production of 13 field isolates from serotypes 1, 5a, 7 and 15 was tested in the presence of sub-MIC of penicillin G using a polystyrene microtiter plate assay. Using microscopy techniques and enzymatic digestion, biofilm architecture and composition were also characterized after exposure to sub-MIC of penicillin G. Sub-MIC of penicillin G significantly induced biofilm formation of nine isolates. The penicillin G-induced biofilms contained more poly-N-acetyl-D-glucosamine (PGA), extracellular DNA and proteins when compared to control biofilms grown without penicillin G. Additionally, penicillin G-induced biofilms were sensitive to DNase which was not observed with the untreated controls. Furthermore, sub-MIC of penicillin G up-regulated the expression of pgaA, which encodes a protein involved in PGA synthesis, and the genes encoding the envelope-stress sensing two-component regulatory system CpxRA. In conclusion, sub-MICs of penicillin G significantly induce biofilm formation and this is likely the result of a cell envelope stress sensed by the CpxRA system resulting in an increased production of PGA and other matrix components. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of balancing methods in modeling the penicillin fermentation.

PubMed

Heijnen, J J; Roels, J A; Stouthamer, A H

1979-12-01

This paper shows the application of elementary balancing methods in combination with simple kinetic equations in the formulation of an unstructured model for the fed-batch process for the production of penicillin. The rate of substrate uptake is modeled with a Monod-type relationship. The specific penicillin production rate is assumed to be a function of growth rate. Hydrolysis of penicillin to penicilloic acid is assumed to be first order in penicillin. In simulations with the present model it is shown that the model, although assuming a strict relationship between specific growth rate and penicillin productivity, allows for the commonly observed lag phase in the penicillin concentration curve and the apparent separation between growth and production phase (idiophase-trophophase concept). Furthermore it is shown that the feed rate profile during fermentation is of vital importance in the realization of a high production rate throughout the duration of the fermentation. It is emphasized that the method of modeling presented may also prove rewarding for an analysis of fermentation processes other than the penicillin fermentation.

Penicillin allergy-getting the label right.

PubMed

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/.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

One-week oral challenge with penicillin in diagnosis of penicillin allergy.

PubMed

Hjortlund, Janni; Mortz, Charlotte Gotthard; Skov, Per Stahl; Eller, Esben; Poulsen, Johan Milling; Borch, Jakob Eli; Bindslev-Jensen, Carsten

2012-05-01

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, 30.0% showed immediate reactions and 5.7% reacted during p.o.7. Approximately 20% of all patients with positive outcome during penicillin challenge are detected by adding p.o.7 with penicillin to the original ENDA guidelines.

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

PubMed Central

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

2013-01-01

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

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

Back to the Future: Penicillin-Susceptible Staphylococcus aureus.

PubMed

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.

Antipneumococcal activities of gemifloxacin compared to those of nine other agents.

PubMed

Davies, T A; Kelly, L M; Pankuch, G A; Credito, K L; Jacobs, M R; Appelbaum, P C

2000-02-01

The activities of gemifloxacin compared to those of nine other agents was tested against a range of penicillin-susceptible and -resistant pneumococci by agar dilution, microdilution, time-kill, and post-antibiotic effect (PAE) methods. Against 64 penicillin-susceptible, 68 penicillin-intermediate, and 75 penicillin-resistant pneumococci (all quinolone susceptible), agar dilution MIC(50)s (MICs at which 50% of isolates are inhibited)/MIC(90)s (in micrograms per milliliter) were as follows: gemifloxacin, 0.03/0.06; ciprofloxacin, 1.0/4.0; levofloxacin, 1.0/2. 0; sparfloxacin, 0.5/1.0; grepafloxacin, 0.125/0.5; trovafloxacin, 0. 125/0.25; amoxicillin, 0.016/0.06 (penicillin-susceptible isolates), 0.125/1.0 (penicillin-intermediate isolates), and 2.0/4.0 (penicillin-resistant isolates); cefuroxime, 0.03/0.25 (penicillin-susceptible isolates), 0.5/2.0 (penicillin-intermediate isolates), and 8.0/16.0 (penicillin-resistant isolates); azithromycin, 0.125/0.5 (penicillin-susceptible isolates), 0. 125/>128.0 (penicillin-intermediate isolates), and 4.0/>128.0 (penicillin-resistant isolates); and clarithromycin, 0.03/0.06 (penicillin-susceptible isolates), 0.03/32.0 (penicillin-intermediate isolates), and 2.0/>128.0 (penicillin-resistant isolates). Against 28 strains with ciprofloxacin MICs of >/=8 microg/ml, gemifloxacin had the lowest MICs (0.03 to 1.0 microg/ml; MIC(90), 0.5 microg/ml), compared with MICs ranging between 0.25 and >32.0 microg/ml (MIC(90)s of 4.0 to >32.0 microg/ml) for other quinolones. Resistance in these 28 strains was associated with mutations in parC, gyrA, parE, and/or gyrB or efflux, with some strains having multiple resistance mechanisms. For 12 penicillin-susceptible and -resistant pneumococcal strains (2 quinolone resistant), time-kill results showed that levofloxacin at the MIC, gemifloxacin and sparfloxacin at two times the MIC, and ciprofloxacin, grepafloxacin, and trovafloxacin at four times the MIC were bactericidal for all strains after 24 h. Gemifloxacin was uniformly bactericidal after 24 h at

Analysis of penicillin G in milk by liquid chromatography.

PubMed

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.

Elucidation of conditions allowing conversion of penicillin G and other penicillins to deacetoxycephalosporins by resting cells and extracts of Streptomyces clavuligerus NP1

PubMed Central

Cho, Hiroshi; Adrio, José L.; Luengo, José M.; Wolfe, Saul; Ocran, Simeon; Hintermann, Gilberto; Piret, Jacqueline M.; Demain, Arnold L.

1998-01-01

Using resting cells and extracts of Streptomyces clavuligerus NP1, we have been able to convert penicillin G (benzylpenicillin) to deacetoxycephalosporin G. Conversion was achieved by increasing by 45× the concentration of FeSO4 (1.8 mM) and doubling the concentration of α-ketoglutarate (1.28 mM) as compared with standard conditions used for the normal cell-free conversion of penicillin N to deacetoxycephalosporin C. ATP, MgSO4, KCl, and DTT, important in cell-free expansion of penicillin N, did not play a significant role in the ring expansion of penicillin G by resting cells or cell-free extracts. When these conditions were used with 14 other penicillins, ring expansion was achieved in all cases. PMID:9751702

Penicillin allergy: value of including amoxicillin as a determinant in penicillin skin testing.

PubMed

Lin, Erina; Saxon, Andrew; Riedl, Marc

2010-01-01

Allergy to penicillins remains an important issue. Penicillin skin testing (PST) with major and minor determinants has been shown to be a highly valuable tool for identifying IgE-mediated penicillin allergy. The value of additional testing with side-chain-specific moieties from semisynthetic penicillins such as amoxicillin is not well-established in spite of the widespread use of these medications. A retrospective review of all consecutive inpatient PST results from 1995 to 2007 comprising 1,068 patients was performed in our institution on individuals with a self-reported history of beta-lactam allergy to assess the importance of including the amoxicillin determinant in a previously validated PST panel. Descriptive statistics were performed. The PST panel included penicilloyl-polylysine, penicillin G, penicilloate, penilloate and amoxicillin. Of 1,068 patients, 243 (23%) had a positive skin test reaction on the PST panel. Testing with amoxicillin was positive in 30.9% of patients, the majority of whom (81%) were also positive to 1 or more standard penicillin reagents. Fourteen of the 243 positive patients (5.8%) had a positive skin test reaction only to amoxicillin. Additionally, the use of penicilloate and penilloate minor determinants in combination with penicillin G identified a greater percentage of penicillin-allergic individuals compared to using only penicillin G (22.6 vs. 6.6%), demonstrating their importance in the PST panel. These data indicate that the inclusion of the amoxicillin determinant appears to identify a small but important group of allergic individuals who may otherwise test negative on a PST panel. Copyright 2010 S. Karger AG, Basel.

Penicillin skin testing in cardiac surgery.

PubMed

Cook, David J; Barbara, David W; Singh, Karen E; Dearani, Joseph A

2014-06-01

Penicillin is the most commonly reported allergy in cardiac surgical patients and a history of penicillin allergy frequently results in the use of vancomycin for antibiotic prophylaxis. However, clinical history is unreliable and true allergy is rare. Penicillin allergy testing has the potential to reduce vancomycin use and indirectly the potential for selection of vancomycin-resistant organisms, a national priority. After the publication of the 2007 Society of Thoracic Surgeons practice guideline report, we initiated a penicillin allergy testing service for cardiac surgical patients in 2009. We sought to determine the true incidence of penicillin allergy in the tested population, whether testing availability reduced vancomycin use in those tested, and if vancomycin use was reduced in the entire cardiac surgical population as a whole. A total of 276 patients were skin tested for allergy to penicillin or cephalosporin. Testing recommended no penicillin use in 13.8% of those tested giving a true penicillin allergy incidence of 0.9%. Only 24 of the 276 patients tested (9%) received vancomycin. However, given the small percentage of the total population that underwent allergy testing, the overall use of vancomycin in the cardiac surgery practice was not reduced in the posttesting period. The true rate of contraindication to penicillin in a cardiac surgical population is very low. Penicillin allergy testing can reduce vancomycin use in the tested population, but better means of conducting the testing and making the results available are necessary to reduce unnecessary vancomycin use in a broader cardiac surgical population. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

A clinical decision-making algorithm for penicillin allergy.

PubMed

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.

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

THE INACTIVATION OF PENICILLINS F, G, K, AND X BY HUMAN AND RABBIT SERUM

PubMed Central

Eagle, Harry

1947-01-01

1. Penicillins F, G, K, and X were all inactivated by human and rabbit serum, but two qualitatively distinct mechanisms were apparently involved. 2. One was a slow inactivation of all four penicillins by a relatively thermostable serum component which was not demonstrably affected by heating for 60 minutes at 56°C. (a) In both human and rabbit serum this general inactivation of penicillin behaved like a pseudo first order reaction, with a velocity constant of 0.05–0.07 for penicillin X, and 0.09–0.11 for penicillins F and G. (b) The percentage of penicillins F, G, and X inactivated per hour was independent of their concentration over the range 0.4 to 50 micrograms per cc., averaging 9.5, 10, and 6.5 per cent, respectively, in human serum, and 9,8.5, and 5 per cent in rabbit serum. (c) The rate of inactivation varied linearly with the concentration of the serum factor. (d) Penicillin X was consistently and significantly less susceptible to inactivation than any of the other penicillins. Although minor differences were observed between F and G, these were not consistent, and are of questionable significance. 3. Superimposed on this slow inactivation of penicillins F, G, K, and X by a thermostable serum component was a much faster inactivation observed only with penicillin K. (a) In both rabbit and human serum, the serum factor responsible for this inactivation was highly thermolabile, and was almost completely destroyed within 5 minutes at 56°C., leaving only a thermostable component, not affected by further heating. (b) The inactivation of K by this thermolabile component was not a first order reaction, but varied with the concentration of both serum and penicillin. At high concentrations of K, the rate of inactivation due to the thermolabile factor was negligible, and penicillin K was destroyed no more rapidly than F, G, or X. The rate of inactivation increased as the concentration of penicillin was reduced. At penicillin K concentrations of 50, 10, 2, and 0.4 micrograms per cc., the hourly destruction in rabbit serum averaged 10, 16, 21, and 54 per cent. The corresponding figures in human serum were 10, 11, 14, and 54 per cent. The reservations entailed by the large serum error at the lower concentrations of penicillin are discussed in the text. 4. The temperature coefficient for the inactivation of penicillin K by fresh human or rabbit serum was 2.5 for each 10°C. No significant inactivation was observed in 24 hours at 20°C.; and this was true also of penicillins F, G, and X. 5. Heparinized plasma was just as active as serum, washed red blood cells had no effect, and the activity of whole blood was referable to its plasma content. 6. The nature of the serum factors responsible for these two types of penicillin inactivation are under present study. 7. The urinary excretion of penicillin is so rapid that the slow destruction of penicillins F, G, and X in the circulating blood as here described is of secondary significance therapeutically. It nevertheless must contribute to their rapid disappearance from the blood; and the fact that X is inactivated more slowly than either F or G could be reflected in higher and more sustained blood levels than are afforded by the latter two species. There are some reports that such is the case (15–17), and the following paper provides further evidence for the superiority of penicillin X in this respect over the other species so far studied. The serum inactivation of penicillin K, at a rate which increases as its concentration falls, should be reflected in significantly lower and more evanescent blood levels than are observed with penicillins F, G, or X. As will be discussed in the following paper, this has been found to be the case, and provides a simple explanation for its paradoxically low therapeutic activity in vivo (8–11). PMID:19871604

Effect of dissolved carbon dioxide on penicillin fermentations: mycelial growth and penicillin production. [Penicillium chrysogenum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, C.S.; Smith, M.D.

The effect of dissolved carbon dioxide on the specific growth rate and the penicillin production rate of Penicillium chrysogenum was examined experimentally. The dissolved carbon dioxide was found to inhibit the specific growth rate and the penicillin production rate when the aerated submerged penicillin fermentation was exposed to influent gases of 12.6 and 20% carbon dioxide, respectively. Upon exposure to influent gases of 3 and 5% carbon dioxide, no pronounced metabolic inhibition was noted.

CROSS-RESISTANCE OF ESCHERICHIA COLI B TO PENICILLIN AND IONIZING RADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kutas-Mannhardt, V.

The radiosensitivity of cultures resistant to 1500 IU/ml, 2000 IU/ml, 2500 IU/ml of penicillin, produced from strain E. coli B was examined. Cultures in the log-phase were streaked in monocellular layers on the agar surface and exposed to x irradiation. As a result of penicillin treatment cell-filaments consisting of several segments were formed. Measurement of viability of x- irradiated cultures proved that penicillin resistant cultures are considerably more radioresistant than the parent strain B, non-treated with penicillin. (auth)

Penicillin and Beta-Lactam Hypersensitivity.

PubMed

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.

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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.

Depletion of penicillin G residues in sows after intramuscular injection

USDA-ARS?s Scientific Manuscript database

The US-FDA CVM has not established a tolerance for penicillin residues in swine tissues, but across much of Europe and Asia a tolerance of 50 ppb penicillin G is in effect. In the US, heavy sows are often treated with extra-label doses of penicillin G, however appropriate pre-slaughter withdrawal p...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin G procaine-dihydrostreptomycin sulfate... INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696c Penicillin G procaine-dihydrostreptomycin sulfate for intramammary infusion (dry cows). (a) Specifications. Each 10 milliliters of suspension contains penicillin G...

21 CFR 526.1696a - Penicillin G procaine.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin G procaine. 526.1696a Section 526.1696a... DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696a Penicillin G procaine. (a) Specifications. Each 10-milliliter single-dose syringe contains penicillin G procaine...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin G procaine-novobiocin for intramammary... DRUGS § 526.1696d Penicillin G procaine-novobiocin for intramammary infusion. (a) Specifications. For lactating cattle: each 10-milliliter dose contains 100,000 units of penicillin G procaine and 150 milligrams...

Depletion of penicillin G residues in sows after intramuscular injection

USDA-ARS?s Scientific Manuscript database

A penicillin G procaine residue depletion study was conducted in heavy sows to estimate the pre-slaughter withdrawal periods necessary to clear penicillin from kidney and muscle. Heavy sows (n = 126) were treated with penicillin G procaine at a 5x dose (33,000 IU/kg) for 3 consecutive days by intra...

21 CFR 526.1696a - Penicillin G procaine.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin G procaine. 526.1696a Section 526.1696a... DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696a Penicillin G procaine. (a) Specifications. Each 10-milliliter single-dose syringe contains penicillin G procaine...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin G procaine-dihydrostreptomycin sulfate... INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696c Penicillin G procaine-dihydrostreptomycin sulfate for intramammary infusion (dry cows). (a) Specifications. Each 10 milliliters of suspension contains penicillin G...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin G procaine-novobiocin for intramammary... DRUGS § 526.1696d Penicillin G procaine-novobiocin for intramammary infusion. (a) Specifications. For lactating cattle: each 10-milliliter dose contains 100,000 units of penicillin G procaine and 150 milligrams...

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin G procaine-dihydrostreptomycin sulfate... INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696c Penicillin G procaine-dihydrostreptomycin sulfate for intramammary infusion (dry cows). (a) Specifications. Each 10 milliliters of suspension contains penicillin G...

77 FR 4895 - New Animal Drugs; Chloramphenicol, Diethylcarbamazine Citrate, Hygromycin B, Methoxyflurane...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-01

... Citrate, Hygromycin B, Methoxyflurane, Neomycin Sulfate, Penicillin G, Phenylbutazone, Pyrantel Tartrate..., (penicillin G Inc., 15 West benzathine, Putnam, penicillin G Porterville, CA procaine). 93257. NADA 095-953... paragraphs (b)(1), (b)(3), (d)(1)(iii), and (d)(2)(iii) to read as follows: Sec. 522.1696a Penicillin G...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin G procaine-novobiocin for intramammary... DRUGS § 526.1696d Penicillin G procaine-novobiocin for intramammary infusion. (a) Specifications. For lactating cattle: each 10-milliliter dose contains 100,000 units of penicillin G procaine and 150 milligrams...

21 CFR 520.1696d - Penicillin V tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin V tablets. 520.1696d Section 520.1696d... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000...

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Neomycin, penicillin, polymyxin B, and... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484h Neomycin, penicillin, polymyxin B, and hydrocortisone suspension... equivalent to 17.5 milligrams of neomycin, 10,000 international units of penicillin G procaine, 5,000...

21 CFR 526.1696a - Penicillin G procaine.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin G procaine. 526.1696a Section 526.1696a... DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696a Penicillin G procaine. (a) Specifications. Each 10-milliliter single-dose syringe contains penicillin G procaine...

21 CFR 526.1696a - Penicillin G procaine.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin G procaine. 526.1696a Section 526.1696a... DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696a Penicillin G procaine. (a) Specifications. Each 10-milliliter single-dose syringe contains penicillin G procaine...

21 CFR 520.1696d - Penicillin V tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin V tablets. 520.1696d Section 520.1696d... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin G procaine-dihydrostreptomycin sulfate... INTRAMAMMARY DOSAGE FORM NEW ANIMAL DRUGS § 526.1696c Penicillin G procaine-dihydrostreptomycin sulfate for intramammary infusion (dry cows). (a) Specifications. Each 10 milliliters of suspension contains penicillin G...

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin G procaine-novobiocin for intramammary... DRUGS § 526.1696d Penicillin G procaine-novobiocin for intramammary infusion. (a) Specifications. For lactating cattle: each 10-milliliter dose contains 100,000 units of penicillin G procaine and 150 milligrams...

Susceptibility of Respiratory Tract Anaerobes to Orally Administered Penicillins and Cephalosporins

PubMed Central

Busch, David F.; Kureshi, Lubna Afzal; Sutter, Vera L.; Finegold, Sydney M.

1976-01-01

Anaerobic bacteria recovered from airway-related infections were tested by agar dilution against selected penicillins and cephalosporins available for oral administration. Against 136 isolates, penicillins G and V showed comparable activity, particularly when pharmacological differences were considered. Although many isolates were exquisitely susceptible to the penicillins, only 55% of the Bacteroides species and 72% of all isolates were inhibited at 0.5 μg of penicillin G per ml. Results for penicillin V at 1 μg/ml were similar (59 and 73%). The two cephalosporins were more active at achievable levels, inhibiting 94 to 95% of Bacteroides and 95 to 96% of all isolates at 8 μg/ml. These levels represent approximately 50% of the reported peak serum levels after oral administration of 625 mg of the penicillins and 500 mg of the cephalosporins. Dicloxacillin and nafcillin were tested against 50 isolates. The two were comparably active on a weight basis; dicloxacillin was more active when pharmacological differences were considered, but did not match the other penicillins or the cephalosporins. PMID:984805

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

PubMed

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 < 0.0001), and there were significantly fewer Asians with 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.

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

PubMed

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.

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

PubMed Central

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 < 0.0001), and there were significantly fewer Asians with 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. PMID:25584917

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

PubMed

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.

Antipneumococcal Activities of Gemifloxacin Compared to Those of Nine Other Agents

PubMed Central

Davies, Todd A.; Kelly, Linda M.; Pankuch, Glenn A.; Credito, Kim L.; Jacobs, Michael R.; Appelbaum, Peter C.

2000-01-01

The activities of gemifloxacin compared to those of nine other agents was tested against a range of penicillin-susceptible and -resistant pneumococci by agar dilution, microdilution, time-kill, and post-antibiotic effect (PAE) methods. Against 64 penicillin-susceptible, 68 penicillin-intermediate, and 75 penicillin-resistant pneumococci (all quinolone susceptible), agar dilution MIC50s (MICs at which 50% of isolates are inhibited)/MIC90s (in micrograms per milliliter) were as follows: gemifloxacin, 0.03/0.06; ciprofloxacin, 1.0/4.0; levofloxacin, 1.0/2.0; sparfloxacin, 0.5/1.0; grepafloxacin, 0.125/0.5; trovafloxacin, 0.125/0.25; amoxicillin, 0.016/0.06 (penicillin-susceptible isolates), 0.125/1.0 (penicillin-intermediate isolates), and 2.0/4.0 (penicillin-resistant isolates); cefuroxime, 0.03/0.25 (penicillin-susceptible isolates), 0.5/2.0 (penicillin-intermediate isolates), and 8.0/16.0 (penicillin-resistant isolates); azithromycin, 0.125/0.5 (penicillin-susceptible isolates), 0.125/>128.0 (penicillin-intermediate isolates), and 4.0/>128.0 (penicillin-resistant isolates); and clarithromycin, 0.03/0.06 (penicillin-susceptible isolates), 0.03/32.0 (penicillin-intermediate isolates), and 2.0/>128.0 (penicillin-resistant isolates). Against 28 strains with ciprofloxacin MICs of ≥8 μg/ml, gemifloxacin had the lowest MICs (0.03 to 1.0 μg/ml; MIC90, 0.5 μg/ml), compared with MICs ranging between 0.25 and >32.0 μg/ml (MIC90s of 4.0 to >32.0 μg/ml) for other quinolones. Resistance in these 28 strains was associated with mutations in parC, gyrA, parE, and/or gyrB or efflux, with some strains having multiple resistance mechanisms. For 12 penicillin-susceptible and -resistant pneumococcal strains (2 quinolone resistant), time-kill results showed that levofloxacin at the MIC, gemifloxacin and sparfloxacin at two times the MIC, and ciprofloxacin, grepafloxacin, and trovafloxacin at four times the MIC were bactericidal for all strains after 24 h. Gemifloxacin was uniformly bactericidal after 24 h at ≤0.5 μg/ml. Various degrees of 90 and 99% killing by all quinolones were detected after 3 h. Gemifloxacin and trovafloxacin were both bactericidal at two times the MIC for the two quinolone-resistant pneumococci. Amoxicillin at two times the MIC and cefuroxime at four times the MIC were uniformly bactericidal after 24 h, with some degree of killing at earlier time points. Macrolides gave slower killing against the seven susceptible strains tested, with 99.9% killing of all strains at two to four times the MIC after 24 h. PAEs for five quinolone-susceptible strains were similar (0.3 to 3.0 h) for all quinolones, and significant quinolone PAEs were found for the quinolone-resistant strain. PMID:10639354

[Evaluation of penicillin-binding protein genotypes in penicillin susceptible and resistant Streptococcus pneumoniae isolates].

PubMed

Aslan, Gönül; Tezcan, Seda; Delialioğlu, Nuran; Aydın, Fatma Esin; Kuyucu, Necdet; Emekdaş, Gürol

2012-04-01

Penicillin-binding proteins (PBPs) are the natural targets of beta-lactam antibiotics and mutations in pbp1a, pbp2b, and pbp2x genes, which encode PBPs, are responsible for resistance to beta-lactams in Streptococcus pneumoniae. In the present study, we intended to determine how often the common mutation patterns occurred within the pbp1a, pbp2b, and pbp2x PBP gene regions and evaluate the PBP genotype mutations which were associated with penicillin resistance in several penicillin-susceptible and - resistant S.pneumoniae isolates in Mersin, Turkey. A total of 62 S.pneumoniae strains isolated from different clinical specimens (32 nasopharyngeal swab, 16 sputum, 3 blood, 3 wound, 2 cerebrospinal fluids and one of each urine, abscess, bronchoalveolar lavage, conjunctival swab, tracheal aspirate, middle ear effusion) were included in the study. Penicillin susceptibilities of the isolates were searched by disc diffusion and E-test methods, and 23 of them were identified as susceptible, 31 were intermediate susceptible, and eight were resistant to penicillin. A rapid DNA extraction procedure was performed for the isolation of nucleic acids from the strains. Distribution of PBP gene mutations in pbp1a, pbp2b, and pbp2x gene regions related to penicillin resistance was determined by using a wild-type specific polymerase chain reaction (PCR) based technique. PBP gene alterations of those isolates were also evaluated in relation to penicillin susceptibility and resistance patterns. Twenty two (95.7%) of 23 penicillin-susceptible S.pneumoniae isolates exhibited no mutation in the three PBP genes (pbp1a, pbp2x, and pbp 2b), while 1 (4.3%) of these harbored mutations in all of the three PBP genes. The penicillin-intermediate susceptible S.pneumoniae isolates exhibited various combinations of mutations. One (3.2%) of 31 penicillin-intermediate susceptible isolates exhibited no mutation in the three PBP genes, while 22 (71%) of them yielded mutations in all of the three PBP genes. The remaining 8 (25.8%) isolates harbored mutations for dual PBP genes (in five strains pbp1a and pbp2b; in two strains pbp2x and pbp2b; in one strain pbp1a and pbp2x). Seven (87.5%) out of eight penicillin-resistant S.pneumoniae isolates (MIC ≥ 2 µg/ml) revealed mutations in all of the three PBP genes and the other penicillin-resistant isolates exhibited no mutation in the PBP genes. The present study supplied important data on the frequency of different patterns of mutations occurring at various regions of PBP genes related to penicillin resistance in S.pneumoniae isolates in our restricted region. The results supported the notion that penicillin resistance in S.pneumoniae was mainly attributed to alterations in pbp1a, pbp2x, and pbp2b gene regions and wild-type sequence specific PCR could be applied to characterize genotypic background of penicillin resistance in S.pneumoniae strains.

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin V potassium for oral solution. 520....1696c Penicillin V potassium for oral solution. (a) Specifications. When reconstituted, each milliliter contains 25 milligrams (40,000 units) of penicillin V. (b) Sponsor. See No. 050604 in § 510.600(c) of this...

21 CFR 520.1696c - Penicillin V powder.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin V powder. 520.1696c Section 520.1696c... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696c Penicillin V powder. (a) Specifications. When reconstituted, each milliliter contains 25 milligrams (40,000 units) of penicillin V. (b...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin V potassium for oral solution. 520....1696c Penicillin V potassium for oral solution. (a) Specifications. When reconstituted, each milliliter contains 25 milligrams (40,000 units) of penicillin V. (b) Sponsor. See No. 050604 in § 510.600(c) of this...

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

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

21 CFR 520.1696b - Penicillin G powder.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin G powder. 520.1696b Section 520.1696b... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696b Penicillin G powder. (a) Specifications. Each gram of powder contains penicillin G potassium equivalent to 1.54 million units of...

21 CFR 520.1696c - Penicillin V powder.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin V powder. 520.1696c Section 520.1696c... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696c Penicillin V powder. (a) Specifications. When reconstituted, each milliliter contains 25 milligrams (40,000 units) of penicillin V. (b...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

21 CFR 520.1696b - Penicillin G powder.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin G powder. 520.1696b Section 520.1696b... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696b Penicillin G powder. (a) Specifications. Each gram of powder contains penicillin G potassium equivalent to 1.54 million units of...

Correlation of Resistance to Proflavine and Penicillin in Escherichia coli

PubMed Central

McKellar, Robin C.; McKenzie, Colin N.; Kushner, Donn J.

1976-01-01

A number of proflavine (PF)-resistant mutants of Escherichia coli B were also resistant to penicillin and cephalothin. Mutants resistant to 1.0 mM PF were 10 times more penicillin resistant than were the PF-susceptible, wild-type cells. Single-step mutants selected for resistance to either PF or penicillin were also resistant to the other drug. None of the resistant mutants tested possessed β-lactamase activity. These results suggest that resistance to PF and penicillin in E. coli B may be due to permeability changes in the cell envelope. PMID:791110

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

PubMed

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.

THE CROSS-RESISTANCE TO PENICILLIN AND RADIATION OF ESCHERICHIA COLI B (in Hungarian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kutas, V.

The radiosensitivity of cultures resistant to 1500 IU/ml, 2000 IU/ml, 2500 IU/ml of penicillin, produced from strain E. coli B was examined. Cultures in the log-phase were streaked in monocellular layers on the agar surface and x irradiation was applied. As a result of penicillin treatment cell filaments consisting of several members were formed. Measuring the effect of ionizing radiation by the percentage survival, the cultures resistant to penicillin proved to be considerably more radioresistant than the parent strain B, non-treated with penicillin. (auth)

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

PubMed

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 < 0.0001), and dementia (P < 0.0001). 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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Preston, D.A.; Wu, C.Y.; Blaszczak, L.C.

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 ({sup 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 ({sup 3}H)penicillin G and locally synthesized ({sup 125}I)penicillin V (IPV) in their recognition of bacterial PBPs. Profilesmore » 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 ({sup 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.« less

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

PubMed

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.

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

PubMed

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

2009-01-01

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

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

PubMed

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

Commonly prescribed β-lactam antibiotics induce C. trachomatis persistence/stress in culture at physiologically relevant concentrations

PubMed Central

Kintner, Jennifer; Lajoie, Dawn; Hall, Jennifer; Whittimore, Judy; Schoborg, Robert V.

2014-01-01

Chlamydia trachomatis, the most common bacterial sexually transmitted disease agent worldwide, enters a viable, non-dividing and non-infectious state (historically termed persistence and more recently referred to as the chlamydial stress response) when exposed to penicillin G in culture. Notably, penicillin G-exposed chlamydiae can reenter the normal developmental cycle upon drug removal and are resistant to azithromycin-mediated killing. Because penicillin G is less frequently prescribed than other β-lactams, the clinical relevance of penicillin G-induced chlamydial persistence/stress has been questioned. The goal of this study was to determine whether more commonly used penicillins also induce C. trachomatis serovar E persistence/stress. All penicillins tested, as well as clavulanic acid, induced formation of aberrant, enlarged reticulate bodies (RB) (called aberrant bodies or AB) characteristic of persistent/stressed chlamydiae. Exposure to the penicillins and clavulanic acid also reduced chlamydial infectivity by >95%. None of the drugs tested significantly reduced chlamydial unprocessed 16S rRNA or genomic DNA accumulation, indicating that the organisms were viable, though non-infectious. Finally, recovery assays demonstrated that chlamydiae rendered essentially non-infectious by exposure to ampicillin, amoxicillin, carbenicillin, piperacillin, penicillin V, and clavulanic acid recovered infectivity after antibiotic removal. These data definitively demonstrate that several commonly used penicillins induce C. trachomatis persistence/stress at clinically relevant concentrations. PMID:24783061

Factors Associated with Loss of Penicillin G Concentrations in Serum After Intramuscular Benzathine Penicillin G Injection: A Meta-analysis

DTIC Science & Technology

2012-07-01

penicillin V in eradication of group a streptococci from children with acute pharyngitis. Pediatrics. 2001;108:1180–1186. 13. Kassem AS, Zaher SR, Abou...Clin Ther. 1959;6:232–241. 38. Zaher SR, Kassem AS, Abou Shleib H, et al. Differences in serum penicillin concentrations following intramuscular

Systemic penicillin as an experimental model of epilepsy.

PubMed

Chen, R C; Huang, Y H; How, S W

1986-06-01

Systemic use of high-dose penicillin was studied in rats and cats to establish an experimental model of epilepsy. In rats, intraperitoneal injection of 2.5 to 5.0 million units/kg (MU/kg) penicillin was effective to induce spikes in 45.7 +/- 31.0 min (means +/- SD) and seizure in 71.5 +/- 38.4 min. In cats, intravenous administration of penicillin at 0.5 to 1.0 MU/kg induced spikes in 10.4 +/- 7.8 min and seizure in 32.2 +/- 19.8 min. Intraperitoneal use of penicillin at 1.0 to 2.0 MU/kg caused spikes in 24.0 +/- 18.4 min and seizure in 71.2 +/- 38.3 min. Pretreatment with intravenous isoniazid at 16.3 +/- 10.3 mg/kg significantly delayed the appearance of intravenous penicillin-induced spikes to 63.1 +/- 49.8 min or prevented the appearance of spikes and abolished the occurrence of seizures. Acupuncture at various points increased the penicillin-induced spikes and seizures.

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

PubMed

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.

Syphilis

MedlinePlus

... tetracycline given to people who are allergic to penicillin) Penicillin G benzathine Length of treatment depends on how ... person's overall health. To treat syphilis during pregnancy, penicillin is the drug of choice. Tetracycline cannot be ...

Engineering deacetoxycephalosporin C synthase as a catalyst for the bioconversion of penicillins.

PubMed

Fan, Keqiang; Lin, Baixue; Tao, Yong; Yang, Keqian

2017-05-01

7-aminodeacetoxycephalosporanic acid (7-ADCA) is a key intermediate of many clinically useful semisynthetic cephalosporins that were traditionally prepared by processes involving chemical ring expansion of penicillin G. Bioconversion of penicillins to cephalosporins using deacetoxycephalosporin C synthase (DAOCS) is an alternative and environmentally friendly process for 7-ADCA production. Arnold Demain and co-workers pioneered such a process. Later, protein engineering efforts to improve the substrate specificity and catalytic efficiency of DAOCS for penicillins have been made by many groups, and a whole cell process using Escherichia coli for bioconversion of penicillins has been developed.

Allergy testing - skin

MedlinePlus

... if you're allergic to bee venom or penicillin. Or it may be used if the skin ... sore, or swollen after contact with the substance Penicillin allergy Venom allergy Allergies to penicillin and related ...

Penicillin V Potassium

MedlinePlus

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 ...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

(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.

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

PubMed

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.

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.

PubMed

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 Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Protective effect of insulin and glucose at different concentrations on penicillin-induced astrocyte death on the primer astroglial cell line☆

PubMed Central

Özdemir, Mehmet Bülent; Akça, Hakan; Erdoğan, Çağdaş; Tokgün, Onur; Demiray, Aydın; Semin, Fenkçi; Becerir, Cem

2012-01-01

Astrocytes perform many functions in the brain and spinal cord. Glucose metabolism is important for astroglial cells and astrocytes are the only cells with insulin receptors in the brain. The common antibiotic penicillin is also a chemical agent that causes degenerative effect on neuronal cell. The aim of this study is to show the effect of insulin and glucose at different concentrations on the astrocyte death induced by penicillin on primer astroglial cell line. It is well known that intracranial penicillin treatment causes neuronal cell death and it is used for experimental epilepsy model commonly. Previous studies showed that insulin and glucose might protect neuronal cell in case of proper concentrations. But, the present study is about the effect of insulin and glucose against astrocyte death induced by penicillin. For this purpose, newborn rat brain was extracted and then mechanically dissociated to astroglial cell suspension and finally grown in culture medium. Clutters were maintained for 2 weeks prior to being used in these experiments. Different concentrations of insulin (0, 1, 3 nM) and glucose (0, 3, 30 mM) were used in media without penicillin and with 2 500 μM penicillin. Penicillin decreased the viability of astroglial cell seriously. The highest cell viability appeared in medium with 3 nM insulin and 3 mM glucose but without penicillin. However, in medium with penicillin, the best cell survival was in medium with 1 nM insulin but without glucose. We concluded that insulin and glucose show protective effects on the damage induced by penicillin to primer astroglial cell line. Interestingly, cell survival depends on concentrations of insulin and glucose strongly. The results of this study will help to explain cerebrovascular pathologies parallel to insulin and glucose conditions of patient after intracranial injuries. PMID:25624816

Documentation of penicillin adverse drug reactions in electronic health records: inconsistent use of allergy and intolerance labels.

PubMed

Inglis, Joshua M; Caughey, Gillian E; Smith, William; Shakib, Sepehr

2017-11-01

The majority of patients with penicillin allergy labels tolerate penicillins. Inappropriate avoidance of penicillin is associated with increased hospitalisation, infections and healthcare costs. To examine the documentation of penicillin adverse drug reactions (ADR) in a large-scale hospital-based electronic health record. Penicillin ADR were extracted from 96 708 patient records in the Enterprise Patient Administration System in South Australia. Expert criteria were used to determine consistency of ADR entry and suitability for further evaluation. Of 43 011 unique ADR reports, there were 5023 ADR to penicillins with most being entered as allergy (n = 4773, 95.0%) rather than intolerance (n = 250, 5.0%). A significant proportion did not include a reaction description (n = 1052, 20.9%). Using pre-set criteria, 10.1% of reports entered as allergy had a reaction description that was consistent with intolerance and 31.0% of the entered intolerances had descriptions consistent with allergy. Virtually all ADR (n = 4979, 99.1%) were appropriate for further evaluation by history taking or immunological testing and half (50.7%, n = 2549) had documented reactions suggesting low-risk of penicillin allergy. The frequency of penicillin allergy label in this data set is consistent with the known overdiagnosis of penicillin allergy in the hospital population. ADR documentation was poor with incomplete entries and inconsistent categorisation. The concepts of allergy and intolerance for ADR classification, whilst mechanistically valid, may not be useful at the point of ADR entry by generalist clinicians. Systematic evaluation of reported ADR is needed to improve the quality of information for future prescribers. © 2017 Royal Australasian College of Physicians.

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

PubMed

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 < .05). Self-reported penicillin allergy was associated with a higher rate of infection, and primarily affected early implant failure.

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

PubMed

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.

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

PubMed

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.

Synergy between baicalein and penicillins against penicillinase-producing Staphylococcus aureus.

PubMed

Qian, Minyi; Tang, Shusheng; Wu, Congming; Wang, Yang; He, Tao; Chen, Tingting; Xiao, Xilong

2015-09-01

The combination of baicalein (the active constituent of Scutellaria baicalensis) with penicillin G/amoxicillin showed potent synergy against 20 clinical penicillinase-producing Staphylococcus aureus strains including 10 isolates that were additionally methicillin-resistant (MRSA). The fractional inhibitory concentration (FIC) indices of penicillins+baiclein ranged from 0.14 to 0.38. Baicalein protected penicillins (penicillin G and amoxicillin) from penicillinase and increased the susceptibility of penicillinase-supplemented S. aureus ATCC 29213 in a dose-dependent manner. The inhibition of penicillinase activity by baicalein should be responsible for the synergism and protective effect. These findings offer us good evidence that the penicillins combined with baicalein showed potent synergistic activity against penicillinase-producing S. aureus and penicillinase-producing MRSA in vitro and might provide promising implications for clinical treatment of these bacterial infections. Copyright © 2015 Elsevier GmbH. All rights reserved.

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

PubMed Central

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

What if Fleming had not discovered penicillin?

PubMed

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.

What if Fleming had not discovered penicillin?

PubMed Central

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

2014-01-01

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. PMID:25183937

The prevalence, population structure and screening test specificity of penicillin-susceptible Staphylococcus aureus bacteremia isolates in Malmö, Sweden.

PubMed

Resman, Fredrik; Thegerström, John; Månsson, Fredrik; Ahl, Jonas; Tham, Johan; Riesbeck, Kristian

2016-08-01

The objectives of this study were to examine the prevalence of penicillin-susceptible bacteremic Staphylococcus aureus in the Malmö area in 2014, to re-evaluate the phenotypic methods of penicillinase detection on these isolates, and to investigate the clonal distribution of penicillin-susceptible isolates. All non-redundant S. aureus from blood in the Malmö catchment area in southern Sweden 2014 were screened for penicillin susceptibility using PcG 1U disk diffusion, E-test PcG and the nitrocefin test. All isolates screened as likely susceptible were subjected to PCR for detection of penicillinase (blaZ) and spa-typing. Almost one out of three bacteremic isolates (80/257; 31.1%) were susceptible to penicillin. All screening methods except for the nitrocefin test alone had a low proportion of isolates falsely tested as susceptible, but no method used in the study had perfect specificity compared with PCR. Penicillin-susceptible isolates had a distinct phylogenetic distribution, and two clonal complexes (CC5 and CC45) constituted half of the isolates. Almost one third of S. aureus isolated from blood in southern Sweden in 2014 was susceptible to penicillin. Considering that intravenous penicillin has theoretical advantages compared with the standard treatment in the study area, we argue that routine testing of penicillin susceptibility should be reconsidered. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Therapeutic significance of penicillin tolerance in experimental streptococcal endocarditis.

PubMed Central

Brennan, R O; Durack, D T

1983-01-01

Tolerance to penicillin exists among the viridans group of streptococci, but its therapeutic significance is unknown. We studied the effect of penicillin alone and in combination with streptomycin, in vivo and in vitro, on three strains of dextran-producing Streptococcus sanguis serotype II which possess widely various degrees of penicillin tolerance. In rabbits with experimental endocarditis, treatment with procaine penicillin (250 mg/kg intramuscularly twice daily for 5 days) decreased the number of viable organisms in valvular vegetations from 8.82 log10 +/- 0.98 CFU/g in untreated controls to 5.31 +/- 1.19 for a highly tolerant strain, 4.22 +/- 1.05 for a less tolerant strain, and 1.79 +/- 1.72 for a nontolerant strain (P less than or equal to 0.01 for comparison between any of the four groups). None of 36 rabbits infected with tolerant strains were cured by 5 days of treatment with penicillin, but 10 of 23 animals infected with the nontolerant strain were cured (P = 0.00002). When streptomycin was given in combination with penicillin, rabbits infected with the nontolerant strain were cured within 3 days, and rabbits infected with the tolerant strain were cured within 5 days. These findings indicate that tolerance can exert a critical influence on the response of S. sanguis to penicillin therapy in vivo and that the combination of penicillin plus streptomycin exerts a synergistic effect against tolerant as well as nontolerant organisms. PMID:6838188

Tissue damage caused by the intramuscular injection of long-acting penicillin.

PubMed

Schanzer, H; Jacobson, J H

1985-04-01

In order to elucidate whether tissue damage produced on occasion by intramuscular injection of long-acting penicillin is due to accidental intra-arterial injection or vasospasm, two types of experiments were carried out in rabbits. In the first set of experiments, six New Zealand White rabbits were given intra-arterial injections of 0.4 mL of a mixture containing 300,000 U of penicillin G benzathine and 300,000 units of penicillin procaine per milliliter (Bicillin C-R) into the left femoral artery and 0.4 mL of normal saline into the right femoral artery as autocontrol. In a second set of experiments, 0.4 mL of the same penicillin preparation was injected in the space surrounding the left femoral artery in five New Zealand rabbits, and 0.4 mL of normal saline was injected in a similar fashion around the right femoral artery as control. The legs of the rabbits that received the intra-arterial injection of penicillin invariably developed ischemic manifestations. None of the legs of rabbits given intra-arterial injections of normal saline had pathologic manifestations. None of the rabbits that received the periarterial penicillin preparation or normal saline developed abnormalities. These results strongly suggest that the tissue damage produced by penicillin is secondary to the intra-arterial administration of the drug.

Penicillin-binding site on the Escherichia coli cell envelope

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

The binding of /sup 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 freemore » 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.« less

Identification of a penicillin-sensitive carboxypeptidase in the cellular slime mold Dictyostelium discoideum.

PubMed

Yasukawa, Hiro; Kuroita, Toshihiro; Tamura, Kentaro; Yamaguchi, Kazuo

2003-07-01

Penicillin binding proteins (PBPs) are penicillin-sensitive DD-peptidases catalyzing the terminal stages of bacterial cell wall assembly. We identified a Dictyostelium discoideum gene that encodes a protein of 522 amino acids showing similarity to Escherichia coli PBP4. The D. discoideum protein conserves three consensus sequences (SXXK, SXN and KTG) that are responsible for the catalytic activities of PBPs. The gene product prepared in the cell-free translation system showed carboxypeptidase activity but the activity was not detected in the presence of penicillin G. These results demonstrate that the D. discoideum gene encodes a eukaryotic form of penicillin-sensitive carboxypeptidase.

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

PubMed

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 < 0.05). The 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.

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

PubMed

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.

Sensitivity of Amoxicillin-Resistant Helicobacter pylori to Other Penicillins

PubMed Central

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

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

PubMed

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.

Galvanostatic Entrapment of Penicillinase into Polytyramine Films and its Utilization for the Potentiometric Determination of Penicillin

PubMed Central

Ismail, Fatma; Adeloju, Samuel B.

2010-01-01

A sensitive and reliable potentiometric biosensor for determination of penicillin has been developed by exploiting the self-limiting growth of the non-conducting polymer, polytyramine. Optimum polytyramine-penicillinase (PTy-PNCnase) films for potentiometric detection of penicillin were accomplished with monomer solutions which contained 0.03 M tyramine, 37 U/mL penicillinase, 0.01 M KNO3, and 3 mM penicillin with an applied current density of 0.8 mA/cm2 and an electropolymerisation time of 40 seconds. The potentiometric biosensor gave a linear concentration range of 3–283 μM for penicillin and achieved a minimum detectable concentration of 0.3 μM. The biosensor was successfully utilized for the detection of Amoxycillin and gave an average percentage recovery of 102 ± 6%. Satisfactory recoveries of penicillin G were also achieved in milk samples with the potentiometric biosensor when concentrations are ≥20 ppm. PMID:22319276

Shared strategies for β-lactam catabolism in the soil microbiome.

PubMed

Crofts, Terence S; Wang, Bin; Spivak, Aaron; Gianoulis, Tara A; Forsberg, Kevin J; Gibson, Molly K; Johnsky, Lauren A; Broomall, Stacey M; Rosenzweig, C Nicole; Skowronski, Evan W; Gibbons, Henry S; Sommer, Morten O A; Dantas, Gautam

2018-06-01

The soil microbiome can produce, resist, or degrade antibiotics and even catabolize them. While resistance genes are widely distributed in the soil, there is a dearth of knowledge concerning antibiotic catabolism. Here we describe a pathway for penicillin catabolism in four isolates. Genomic and transcriptomic sequencing revealed β-lactamase, amidase, and phenylacetic acid catabolon upregulation. Knocking out part of the phenylacetic acid catabolon or an apparent penicillin utilization operon (put) resulted in loss of penicillin catabolism in one isolate. A hydrolase from the put operon was found to degrade in vitro benzylpenicilloic acid, the β-lactamase penicillin product. To test the generality of this strategy, an Escherichia coli strain was engineered to co-express a β-lactamase and a penicillin amidase or the put operon, enabling it to grow using penicillin or benzylpenicilloic acid, respectively. Elucidation of additional pathways may allow bioremediation of antibiotic-contaminated soils and discovery of antibiotic-remodeling enzymes with industrial utility.

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

PubMed

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

Assessment of the susceptibility of Streptococcus pneumoniae to cefaclor and loracarbef in 13 countries.

PubMed

Bandak, S I; Turnak, M R; Allen, B S; Bolzon, L D; Preston, D A

2000-08-01

Between July 1998 and July 1999, 2,644 clinical isolates of Streptococcus pneumoniae were collected from 27 study centers in 13 countries and their susceptibilities to penicillin, cefaclor and loracarbef were determined by E-test" (AB BIODISK, Solna, Sweden). Overall, 96.3% of isolates were penicillin-susceptible (79.8%) or -intermediate (16.6%) (MIC, < or = 1 microg/ml). Rates of penicillin-resistant S. pneumoniae isolation varied widely and were highest in the study centers tested in New Zealand (10.9%), Canada (10.0%), Mexico (9.1%) and the United States (5.1%). Low rates of penicillin-resistance were found in the study centers tested in Russia (0%), Turkey (0%), Brazil (0.5%), Germany (0.6%), Philippines (1.6%), Italy (2.1%), United Kingdom (2.3%), Australia (3.0%) and Poland (3.1%). Using recently published NCCLS interpretative breakpoints (M100-S10, 2000), 87.2% (median) of all isolates tested were cefaclor-susceptible and 87.8% (median) of all isolates tested were loracarbef-susceptible. Of the penicillin-susceptible S. pneumoniae isolates, 99.5% were susceptible to both cefaclor and loracarbef. Susceptibility to cefaclor and loracarbef was also retained by 30.8% and 32.9% of penicillin-intermediate isolates, respectively. These findings are in contrast to recent publications reporting lower cefaclor and loracarbef activities using non-validated interpretative criteria. In conclusion, rates of penicillin resistance among recent clinical isolates of pneumococci remain low in many centers worldwide. Cefaclor and loracarbef demonstrated excellent in vitro activity against recent clinical isolates of penicillin-susceptible and many isolates of penicillin-intermediate S. pneumoniae.

The Cost of Penicillin Allergy Evaluation.

PubMed

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.

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

PubMed

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 <0.25 mg/L or≥0.25 mg/L, except for the ST342. The isolates with penicillin MIC <0.25 mg/L were mainly collected before 2001, after which the isolates with MIC≥0.25 mg/L occurred and became the major population gradually. This law of year distribution, however, was not obvious for any specific ST. The isolates covering by any given ST could be determined with different 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.

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

77 FR 50462 - Foreign-Trade Zone 59-Lincoln, NE, Notification of Proposed Production Activity; Novartis...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-21

... mixed medicines, including those containing penicillin, alkaloids, analgesics, antibiotics....; isradipine (USP); desiccant; croscarmellose sodium NF; microcellulose; bulk penicillin mixed medicines; bulk mixed drugs; including penicillins; antibiotics; hormones; and alkaloids; caffeine; dextrins and...

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

Treatment of experimental pneumonia due to penicillin-resistant Streptococcus pneumoniae in immunocompetent rats.

PubMed Central

Gavaldà, J; Capdevila, J A; Almirante, B; Otero, J; Ruiz, I; Laguarda, M; Allende, H; Crespo, E; Pigrau, C; Pahissa, A

1997-01-01

A model of pneumonia due to Streptococcus pneumoniae resistant to penicillin was developed in immunocompetent Wistar rats and was used to evaluate the efficacies of different doses of penicillin, cefotaxime, cefpirome, and vancomycin. Adult Wistar rats were challenged by intratracheal inoculation with 3 x 10(9) CFU of one strain of S. pneumoniae resistant to penicillin (MICs of penicillin, cefotaxime, cefpirome, and vancomycin, 2, 1, 0.5, and 0.5 microg/ml, respectively) suspended in brain heart broth supplemented with 0.7% agar. The rats experienced a fatal pneumonia, dying within 5 days and with peak mortality (70 to 80%) occurring 48 to 72 h after infection, and the bacterial counts in the lungs persisted from 8.87 +/- 0.3 log10 CFU/g of lung at 24 h of the infection to 9.1 +/- 0.3 log10 CFU/g at 72 h. Four hours after infection the animals were randomized into the following treatment groups: (i) control without treatment, (ii) penicillin G at 100,000 IU/kg of body weight every 2 h, (iii) penicillin G at 250,000 IU/kg every 2 h, (iv) cefotaxime at 100 mg/kg every 2 h, (v) cefpirome at 200 mg/kg every 2 h, and (vi) vancomycin at 50 mg/kg every 8 h. Two different protocols were used for the therapeutic efficacy studies: four doses of beta-lactams and one dose of vancomycin or eight doses of beta-lactams and two doses of vancomycin. Results of the therapy for experimental pneumonia caused by penicillin-resistant S. pneumoniae showed that initially, all the antimicrobial agents tested had similar efficacies, but when we prolonged the treatment, higher doses of penicillin, cefotaxime, and cefpirome were more effective than penicillin at lower doses in decreasing the residual bacterial titers in the lungs. Also, when we extended the treatment, vancomycin was more efficacious than penicillin at lower doses but was less efficacious than higher doses of penicillin or cefpirome. The model that we have developed is simple and amenable for inducing pneumonia in immunocompetent rats and could be used to explore the pathophysiology and to evaluate optimal therapy of this infection in the immunocompetent host. PMID:9087492

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

NASA Astrophysics Data System (ADS)

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.

Microbiological Activities of Lysostaphin and Penicillins Against Bacteriophage 80/81 Strains of Staphylococcus aureus

PubMed Central

Zygmunt, Walter A.; Harrison, Edward F.; Browder, Henry P.

1965-01-01

Using 20 clinical isolates of S. aureus (all bacteriophage 80/81 type), we found that lysostaphin inhibits the growth of all cultures at concentrations significantly lower than those observed with any of eight penicillins, a penicillin-like compound (cephalothin), or fusidic acid (a steroid antibiotic). All test cultures were shown to be resistant to penicillin G, ampicillin, and propicillin. Of the remaining penicillins (all penicillinase-insensitive), oxacillin, nafcillin, cloxacillin, and cephalothin were approximately equal in antimicrobial activity. Ancillin was slightly less active, and methicillin was even lower in potency. Cultures varied more widely in susceptibility to fusidic acid. None of the clinical isolates tested was found to be resistant to lysostaphin. PMID:14325294

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

PubMed

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

2017-09-01

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 and cause adverse reactions in consumers. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model to predict drug residues in edible tissues and estimate extended withdrawal intervals for penicillin G in swine and cattle. A flow-limited PBPK model was developed with data from Food Animal Residue Avoidance Databank using Berkeley Madonna. The model predicted observed drug concentrations in edible tissues, including liver, muscle, and kidney for penicillin G both in swine and cattle well, including data not used in model calibration. For extralabel use (5× and 10× label dose) of penicillin G, Monte Carlo sampling technique was applied to predict times needed for tissue concentrations to fall below established tolerances for the 99th percentile of the population. This model provides a useful tool to predict tissue residues of penicillin G in swine and cattle to aid food safety assessment, and also provide a framework for extrapolation to other food animal species. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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 < 0.001). Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of 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 < 0.001). Cases involving staphylococci, Pseudomonas spp. and Enterobacteriaceae were under-reported. Among 51 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 < 0.05; logistic regression). Other factors that correlated with severe sequelae by univariate analysis only were inappropriate clinical handling, abnormal consciousness, convulsions and nosocomial infection. Overall, the data indicated that neither age alone, community-acquired infection nor absence of identified risk factors can predict susceptibility to penicillin accurately. Recommendations for empirical antibiotic treatment for ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting.

Hydrolysis of penicillins and related compounds by the cell-bound penicillin acylase of Escherichia coli

PubMed Central

Cole, M.

1969-01-01

1. A method is given for the preparation of penicillin acylase by using Escherichia coli N.C.I.B. 8743 and a strain selected for higher yield. The enzyme is associated with the bacterial cells and removes the side chains of penicillins to give 6-amino-penicillanic acid and a carboxylic acid. 2. The rates of penicillin deacylation indicated that p-hydroxybenzylpenicillin was the best substrate, followed in diminishing order by benzyl-, dl-α-hydroxybenzyl-, 2-furylmethyl-, 2-thienylmethyl-, d-α-aminobenzyl-, n-propoxymethyl- and isobutoxymethyl-penicillin. Phenylpenicillin and dl-α-carboxybenzylpenicillin were not substrates and phenoxymethyl-penicillin was very poor. 3. Amides and esters of the above penicillins were also substrates for the deacylation reaction, as were cephalosporins with a thienylmethyl side chain. 4. For the deacylation of 2-furylmethylpenicillin at 21° the optimum pH was 8·2. The optimum temperature was 60° at pH7. 5. By using selection A of N.C.I.B. 8743 and determining reaction velocities by assaying yields of 6-amino-penicillanic acid in a 10min. reaction at 50° and pH8·2, the Km for benzylpenicillin was found to be about 30mm and the Km for 2-furylmethylpenicillin, about 10mm. The Vmax. values were 0·6 and 0·24μmole/min./mg. of bacterial cells respectively. PMID:4982417

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

PubMed

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.

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

PubMed

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, P<0·0001). There was no difference in the onset of symptoms before hospital admission between the two groups (6·5±3·0 vs. 7·7±4·7, P=0·33). Systolic blood pressure was lower in the penicillin 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 (P<0·05). Mortality was similar in both groups (11·6% vs. 13·7%, P=0·60). Treatment of leptospirosis with antibiotics, including the penicillin, 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.

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

PubMed Central

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 of maternal syphilis are important for congenital syphilis prevention, and will be increasingly critical in the future as more countries move toward elimination targets. PMID:27434236

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

PubMed

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

2016-01-01

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. 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. 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. 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 of maternal syphilis are important for congenital syphilis prevention, and will be increasingly critical in the future as more countries move toward elimination targets.

Proteome Analysis of the Penicillin Producer Penicillium chrysogenum

PubMed Central

Jami, Mohammad-Saeid; Barreiro, Carlos; García-Estrada, Carlos; Martín, Juan-Francisco

2010-01-01

Proteomics is a powerful tool to understand the molecular mechanisms causing the production of high penicillin titers by industrial strains of the filamentous fungus Penicillium chrysogenum as the result of strain improvement programs. Penicillin biosynthesis is an excellent model system for many other bioactive microbial metabolites. The recent publication of the P. chrysogenum genome has established the basis to understand the molecular processes underlying penicillin overproduction. We report here the proteome reference map of P. chrysogenum Wisconsin 54-1255 (the genome project reference strain) together with an in-depth study of the changes produced in three different strains of this filamentous fungus during industrial strain improvement. Two-dimensional gel electrophoresis, peptide mass fingerprinting, and tandem mass spectrometry were used for protein identification. Around 1000 spots were visualized by “blue silver” colloidal Coomassie staining in a non-linear pI range from 3 to 10 with high resolution, which allowed the identification of 950 proteins (549 different proteins and isoforms). Comparison among the cytosolic proteomes of the wild-type NRRL 1951, Wisconsin 54-1255 (an improved, moderate penicillin producer), and AS-P-78 (a penicillin high producer) strains indicated that global metabolic reorganizations occurred during the strain improvement program. The main changes observed in the high producer strains were increases of cysteine biosynthesis (a penicillin precursor), enzymes of the pentose phosphate pathway, and stress response proteins together with a reduction in virulence and in the biosynthesis of other secondary metabolites different from penicillin (pigments and isoflavonoids). In the wild-type strain, we identified enzymes to utilize cellulose, sorbitol, and other carbon sources that have been lost in the high penicillin producer strains. Changes in the levels of a few specific proteins correlated well with the improved penicillin biosynthesis in the high producer strains. These results provide useful information to improve the production of many other bioactive secondary metabolites. PMID:20154335

The role of the media in influencing public attitudes to penicillin during World War II.

PubMed

Shama, Gilbert

2015-01-01

Penicillin's trajectory towards becoming an effective antibacterial chemotherapeutic agent took place during World War II. Its strategic military value was immediately recognised by the Allies, and mass production was undertaken with the prime objective of meeting the needs of the armed forces. News of its development came to be widely reported on in the media and is examined here. These reports frequently combined accounts of penicillin's prodigious clinical effectiveness with the fact that it was to remain unavailable to the civilian population essentially until the war had ended. More penicillin was to be made available to the civilian population in the United States than in Britain, but the sense that it was severely rationed remained as high. It was in response to this that the idea of "homemade penicillin" was hatched. News of this was also widely promulgated by both the British and American media. Although the numbers treated with penicillin produced in this way was never to be significant, knowledge of the existence of such endeavours may have served to assuage in some measure the feelings of frustration felt by the civilian population at penicillin's non-availability.

Antimicrobial resistance among lower respiratory tract isolates of Streptococcus pneumoniae: results of a 1992-93 western Europe and USA collaborative surveillance study. The Alexander Project Collaborative Group.

PubMed

Goldstein, F W; Acar, J F

1996-07-01

One thousand, eight hundred and fifty-six Streptococcus pneumoniae strains, collected in 1992 and 1993 from 15 centres in Western Europe and USA were tested for susceptibility to 16 antibiotics. The overall resistance to penicillin was 23% (range 6-54%), with the highest prevalences in Madrid, Barcelona, Toulouse and Cleveland. Seven centres reported low-level penicillin resistance only. Amoxycillin was more active than ceftriaxone against strains with intermediate resistance to penicillin, and at least four-fold more active than cefuroxime; cefaclor and cefixime had poor activity. Against penicillin-resistant strains, ceftriaxone was slightly more active than amoxycillin, cefuroxime exhibited borderline activity and cefixime and cefaclor were inactive. Ten strains fully susceptible to penicillin had MICs of ceftriaxone > or = 0.1 mg/L; this may represent a first step towards the development of cephalosporin resistance. With the exception of fluoroquinolones, resistance to non-beta-lactam antibiotics (chloramphenicol, doxycycline, co-trimoxazole, erythromycin, clarithromycin and azithromycin) was considerably higher in penicillin-resistant strains compared with penicillin-susceptible isolates. Erythromycin-resistant isolates were also resistant to the other macrolides tested.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rathinaswamy, Priya; Pundle, Archana V.; Prabhune, Asmita A.

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.more » Diffraction data were collected under cryogenic conditions to a spacing of 2.5 Å. The crystals belonged to the orthorhombic space group C222{sub 1}, with unit-cell parameters a = 111.0, b = 308.0, c = 56.0 Å. The estimated Matthews coefficient was 3.23 Å{sup 3} Da{sup −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.« less

Production of anti-amoxicillin ScFv antibody and simulation studying its molecular recognition mechanism for penicillins.

PubMed

Liu, Jing; Zhang, Hui C; Duan, Chang F; Dong, Jun; Zhao, Guo X; Wang, Jian P; Li, Nan; Liu, Jin Z; Li, Yu W

2016-11-01

The molecular recognition mechanism of an antibody for its hapten is very interesting. The objective of this research was to study the intermolecular interactions of an anti-amoxicillin antibody with penicillin drugs. The single chain variable fragment (ScFv) antibody was generated from a hybridoma cell strain excreting the monoclonal antibody for amoxicillin. The recombinant ScFv antibody showed similar recognition ability for penicillins to its parental monoclonal antibody: simultaneous recognizing 11 penicillins with cross-reactivities of 18-107%. The three-dimensional structure of the ScFv antibody was simulated by using homology modeling, and its intermolecular interactions with 11 penicillins were studied by using molecular docking. Results showed that three CDRs are involved in antibody recognition; CDR L3 Arg 100, CDR H3 Tyr226, and CDR H3 Arg 228 were the key contact amino acid residues; hydrogen bonding was the main antibody-drug intermolecular force; and the core structure of penicillin drugs was the main antibody binding position. These results could explain the recognition mechanism of anti-amoxicillin antibody for amoxicillin and its analogs. This is the first study reporting the production of ScFv antibody for penicillins and stimulation studying its recognition mechanism.

INACTIVATION OF SOME SEMISYNTHETIC PENICILLINS BY GRAM-NEGATIVE BACILLI

PubMed Central

Sabath, Leon; Finland, Maxwell

1963-01-01

Sabath, Leon (Boston City Hospital, Boston, Mass.) and Maxwell Finland. Inactivation of some semisynthetic penicillins by gram-negative bacilli. J. Bacteriol. 85:314–321. 1963.—An agar diffusion method was used to test 55 strains of gram-negative bacilli for their ability to inactivate penicillin G, methicillin, biphenylpenicillin, oxacillin, and ampicillin; 26 strains inactivated one or more of them. All strains of Klebsiella-Aerobacter, nearly all of Escherichia coli, and some of Pseudomonas aeruginosa, but not those of Proteus or Salmonella, were active by this method. Penicillin G was inactivated by the largest number of strains, biphenylpenicillin and ampicillin by somewhat fewer, and oxacillin and methicillin by about half as many. When the five penicillins were incubated with four strains of different bacteria in broth at 37 C, all were inactivated to a considerable extent by all the strains, each penicillin to a different degree, but to about the same extent by all the strains. Adsorption alone did not account for the loss of activity. The results suggest that there are qualitative, as well as quantitative, differences among species or even strains of gram-negative bacilli in their ability to inactivate the various penicillins. Images PMID:13975857

Rate of penicillin killing of Staphylococcus aureus and Autobac 1 susceptibility test results.

PubMed Central

Harris, J A; Furtado, D

1982-01-01

A clinical isolate of Staphylococcus aureus interpreted as resistant to penicillin by the Autobac 1 susceptibility testing method (i.e., light-scattering index of 0.77) was found to be susceptible to penicillin by both the disk diffusion and broth dilution techniques. The growth rate of the clinical isolate during a 4-h incubation interval was similar to that of a known sensitive reference strain (S. aureus ATCC 25923) used as a control organism for the Autobac test. The bactericidal effect of penicillin was evaluated by measuring the rate of killing over a 4-h interval. The percentages of organisms surviving exposure to 5.0 or 2.5 U of penicillin G per ml (number of organisms recovered at 3 h/number of organisms introduced as inoculum) were 68 and 76%, respectively, for the clinical isolate and 15 and 21%, respectively, for the reference strain. After 24 h of incubation, penicillin was bactericidal for both strains. The need to increase the time of incubation for those S. aureus isolates resistant to penicillin after 3 h of standard incubation time in the Autobac system is discussed. PMID:7068821

21 CFR 558.55 - Amprolium.

Code of Federal Regulations, 2010 CFR

2010-04-01

... obsignata) Feed according to subtable in item (i) Penicillin 2.4 to 50 Replacement chickens; development of active immunity to coccidiosis; growth promotion and feed efficiency As procaine penicillin. Feed... worms (Capillaria obsignata) Feed according to subtable in item (i) Penicillin 2.4 to 50 Broiler...

Screening and productivity of penicillin antibiotic from Penicillium sp.

PubMed

Sivakumari, V; Dhinakaran, J; Rajendran, A

2009-10-01

This paper highlights the antagonism effect of Penicillium isolates, which were screened against the test organisms such as Staphylococcus aureus, E. coli and Penicillium sp. Penicillium notatum and Penicillium chrysogenum isolates were used for penicillin biosynthesis. The antibacterial activities of fermented crude penicillin extract were assayed by disc diffusion method. Maximum antibacterial activity was observed in Gram positive organisms (Staphylococcus aureus) when compared with Gram negative organisms. The isolated Penicillium chrysogenum can be used for large-scale penicillin antibiotic production.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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 < 0.0001). Patients with a 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.

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

PubMed

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 < .05). There is an overall limited understanding of the management of patients with a history of 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.

A population pharmacokinetic modeling approach shows that serum penicillin G concentrations are below inhibitory concentrations by two weeks after benzathine penicillin G injection in the majority of young adults.

PubMed

Neely, Michael; Kaplan, Edward L; Blumer, Jeffrey L; Faix, Dennis J; Broderick, Michael P

2014-11-01

Serum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of >0.02 mg/liter, a proposed protective threshold against group A Streptococcus pyogenes (GAS). The final population model included linear absorption into a central compartment, distribution to and from a peripheral compartment, and linear elimination from the central compartment, with allometrically scaled volumes and rate constants. With 1.2 million units of BPG given intramuscularly every 4 weeks in four total doses, only 23.2% of 5,000 simulated patients maintained serum penicillin G trough concentrations of >0.02 mg/liter 4 weeks after the last dose. When the doses were 1.8 million units and 2.4 million units, the percentages were 30.2% and 40.7%, respectively. With repeated dosing of 1.2 million units every 3 weeks and every 2 weeks for 4 doses, the percentages of simulated patients with a penicillin G trough concentration of >0.02 mg/liter were 37.8% and 65.2%, respectively. Our simulations support recommendations for more frequent rather than higher BPG doses to prevent recurrent rheumatic heart disease in areas of high GAS prevalence or during outbreaks. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

A Population Pharmacokinetic Modeling Approach Shows that Serum Penicillin G Concentrations Are Below Inhibitory Concentrations by Two Weeks after Benzathine Penicillin G Injection in the Majority of Young Adults

PubMed Central

Kaplan, Edward L.; Blumer, Jeffrey L.; Faix, Dennis J.; Broderick, Michael P.

2014-01-01

Serum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of >0.02 mg/liter, a proposed protective threshold against group A Streptococcus pyogenes (GAS). The final population model included linear absorption into a central compartment, distribution to and from a peripheral compartment, and linear elimination from the central compartment, with allometrically scaled volumes and rate constants. With 1.2 million units of BPG given intramuscularly every 4 weeks in four total doses, only 23.2% of 5,000 simulated patients maintained serum penicillin G trough concentrations of >0.02 mg/liter 4 weeks after the last dose. When the doses were 1.8 million units and 2.4 million units, the percentages were 30.2% and 40.7%, respectively. With repeated dosing of 1.2 million units every 3 weeks and every 2 weeks for 4 doses, the percentages of simulated patients with a penicillin G trough concentration of >0.02 mg/liter were 37.8% and 65.2%, respectively. Our simulations support recommendations for more frequent rather than higher BPG doses to prevent recurrent rheumatic heart disease in areas of high GAS prevalence or during outbreaks. PMID:25182635

Lobar pneumonia treated by Musgrave Park physicians.

PubMed

Hedley-Whyte, John; Milamed, Debra R

2009-05-01

In the decade 1935-45 the treatment of lobar pneumonia in the developed and warring world underwent a series of evolutions-anti-sera, specific anti-sera, refinement of sulpha drugs, sulpha and anti-sera, the introduction of penicillin for bacteriology, then ophthalmology, and then for penicillin-sensitive bacterial infections such as lobar pneumonia with its many Cooper types of Streptococcus pneumoniae. Penicillin for civilian use was essentially banned in World War II, a ban that early in 1941 two Musgrave Park physicians tried to circumvent. Strict secrecy on the details of penicillin production was enforced. The treatment option chosen by the Musgrave Park physicians in 1941, and the non-availability of penicillin led to sequelae affecting the post-Belfast careers of both patient and physicians.

Effect of levetiracetam on penicillin induced epileptic activity in rats.

PubMed

Arık, Aliye Erguvan; Bağırıcı, Faruk; Sefil, Fatih; Marangoz, Cafer

2014-01-01

The aim of this study was to investigate the effects of levetiracetam (LEV) on penicillin-induced epileptiform activity in rats. Penicillin was applied intracerebroventricularly (icv) at a dose of 500 IU to induce epileptiform activity. LEV was given intraperitoneally (ip) at doses of 20, 40, 80 mg/kg before penicillin injection. This agent reduced epileptiform activity by decreasing spike frequencies. The mean spike frequencies decreased significantly in all the LEV treated groups. There was no significant change in the spike amplitudes of the LEV groups compared with the control group. 40 mg/kg of LEV was determined as the most effective dose on reducing epileptiform activity. The results of this study suggest that LEV is an effective antiepileptic agent in penicillin-induced epilepsy.

21 CFR 520.1696 - Penicillin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin. 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. ...

21 CFR 520.1696 - Penicillin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin. 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. ...

21 CFR 558.55 - Amprolium.

Code of Federal Regulations, 2013 CFR

2013-04-01

... obsignata) Feed according to subtable in item (i) Penicillin 2.4 to 50 Replacement chickens; development of active immunity to coccidiosis; growth promotion and feed efficiency As procaine penicillin. Feed... to subtable in item (i) Penicillin 2.4 to 50 Broiler chickens; prevention of coccidiosis caused by E...

21 CFR 558.55 - Amprolium.

Code of Federal Regulations, 2011 CFR

2011-04-01

... obsignata) Feed according to subtable in item (i) Penicillin 2.4 to 50 Replacement chickens; development of active immunity to coccidiosis; growth promotion and feed efficiency As procaine penicillin. Feed... to subtable in item (i) Penicillin 2.4 to 50 Broiler chickens; prevention of coccidiosis caused by E...

21 CFR 558.55 - Amprolium.

Code of Federal Regulations, 2012 CFR

2012-04-01

... obsignata) Feed according to subtable in item (i) Penicillin 2.4 to 50 Replacement chickens; development of active immunity to coccidiosis; growth promotion and feed efficiency As procaine penicillin. Feed... to subtable in item (i) Penicillin 2.4 to 50 Broiler chickens; prevention of coccidiosis caused by E...

21 CFR 558.274 - Hygromycin B.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Bacitracin plus penicillin (100 to 200 of combination) 1. Chickens; control of infestation of large...) Feed containing not less than 25% of penicillin plus not less than 50% of bacitracin; as procaine penicillin plus bacitracin methylene disalicylate; withdraw 3 days before slaughter 2. Chickens; control of...

21 CFR 558.274 - Hygromycin B.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Bacitracin plus penicillin (100 to 200 of combination) 1. Chickens; control of infestation of large...) Feed containing not less than 25% of penicillin plus not less than 50% of bacitracin; as procaine penicillin plus bacitracin methylene disalicylate; withdraw 3 days before slaughter 2. Chickens; control of...

Fabrication of a highly sensitive penicillin sensor based on charge transfer techniques.

PubMed

Lee, Seung-Ro; Rahman, M M; Sawada, Kazuaki; Ishida, Makoto

2009-03-15

A highly sensitive penicillin biosensor based on a charge-transfer technique (CTTPS) has been fabricated and demonstrated in this paper. CTTPS comprised a charge accumulation technique for penicilloic acid and H(+) ions perception system. With the proposed CTTPS, it is possible to amplify the sensing signals without external amplifier by using the charge accumulation cycles. The fabricated CTTPS exhibits excellent performance for penicillin detection and exhibit a high-sensitivity (47.852 mV/mM), high signal-to-noise ratio (SNR), large span (1445 mV), wide linear range (0-25 mM), fast response time (<3s), and very good reproducibility. A very lower detection limit of about 0.01 mM was observed from the proposed sensor. Under optimum conditions, the proposed CTTPS outstripped the performance of the widely used ISFET penicillin sensor and exhibited almost eight times greater sensitivity as compared to ISFET (6.56 mV/mM). The sensor system is implemented for the measurement of the penicillin concentration in penicillin fermentation broth.

The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use

PubMed Central

2017-01-01

After just over 75 years of penicillin’s clinical use, the world can see that its impact was immediate and profound. In 1928, a chance event in Alexander Fleming’s London laboratory changed the course of medicine. However, the purification and first clinical use of penicillin would take more than a decade. Unprecedented United States/Great Britain cooperation to produce penicillin was incredibly successful by 1943. This success overshadowed efforts to produce penicillin during World War II in Europe, particularly in the Netherlands. Information about these efforts, available only in the last 10–15 years, provides new insights into the story of the first antibiotic. Researchers in the Netherlands produced penicillin using their own production methods and marketed it in 1946, which eventually increased the penicillin supply and decreased the price. The unusual serendipity involved in the discovery of penicillin demonstrates the difficulties in finding new antibiotics and should remind health professionals to expertly manage these extraordinary medicines.

Treatment of Gonorrhea with Spectinomycin Hydrochloride: Comparison with Standard Penicillin Schedules

PubMed Central

Duncan, W. Christopher; Holder, William R.; Roberts, David P.; Knox, John M.

1972-01-01

Spectinomycin hydrochloride, a new parenteral antibiotic prepared from Streptomyces spectabilis, was compared with standard U.S. Public Health Service-recommended dosages of aqueous procaine penicillin G in the treatment of uncomplicated gonorrhea in 353 men and 314 women. Of the 314 women, 130 had a pretreatment positive rectal culture. All diagnoses were proven by culture on Thayer-Martin selective medium. Minimal inhibitory concentrations of both drugs were determined. Single doses of 2 and 4 g of spectinomycin were compared with 2.4 million units of procaine penicillin in males and with both 2.4 and 4.8 million units of procaine penicillin in females. Both spectinomycin schedules, 2.4 million units of penicillin in males and 4.8 million units of penicillin in females, resulted in cure rates in excess of 90%. There were no failures at the rectal site only in those women with positive rectal cultures. There was no advantage to using the larger amount of spectinomycin in either sex. PMID:4261553

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

PubMed

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.

Penicillin skin testing: potential implications for antimicrobial stewardship.

PubMed

Unger, Nathan R; Gauthier, Timothy P; Cheung, Linda W

2013-08-01

As the progression of multidrug-resistant organisms and lack of novel antibiotics move us closer toward a potential postantibiotic era, it is paramount to preserve the longevity of current therapeutic agents. Moreover, novel interventions for antimicrobial stewardship programs are integral to combating antimicrobial resistance worldwide. One unique method that may decrease the use of second-line antibiotics (e.g., fluoroquinolones, vancomycin) while facilitating access to a preferred β-lactam regimen in numerous health care settings is a penicillin skin test. Provided that up to 10% of patients have a reported penicillin allergy, of whom ~10% have true IgE-mediated hypersensitivity, significant potential exists to utilize a penicillin skin test to safely identify those who may receive penicillin or a β-lactam antibiotic. In this article, we provide information on the background, associated costs, currently available literature, pharmacists' role, antimicrobial stewardship implications, potential barriers, and misconceptions, as well as future directions associated with the penicillin skin test. © 2013 Pharmacotherapy Publications, Inc.

Chromatography of Penicillins, Penicilloates, and Penicilloylamides on Dextran Gels

PubMed Central

Hyslop, Newton E.; Milligan, Richard J.

1974-01-01

The factors influencing the chromatographic behavior on dextran gels of penicillins and their derivatives were investigated by comparing elution profiles and partition coefficients (KD and KAV) of penicillins differing in side-chain structure and among penicillin derivatives of identical side-chain but different nuclear structure. Under the conditions of pH and ionic strength employed (pH 7.4, 0.145 M NaCl, 0.05 M PO4), side-chain adsorptive effects best explained the anomalous behavior of benzylpenicillin and of oxacillin and its chlorine-substituted analogues. Polar side-chain substituents, such as the amino group of ampicillin and the carboxyl group of carbenicillin, and cleavage of the β-lactam ring, exemplified by penicilloates and penicilloylamines, both appeared to interfere with side-chain-directed adsorption. The differential adsorption of penicillins and their derivatives to dextran gels is not only of theoretical interest relative to the mechanism of chromatography but of practical application to analytical and preparative procedures in penicillin chemistry. PMID:15825415

The role of beta-lactamase in staphylococcal resistance to penicillinase-resistant penicillins and cephalosporins.

PubMed Central

McDougal, L K; Thornsberry, C

1986-01-01

We showed that most Staphylococcus aureus strains that have borderline or intermediate susceptibility to the penicillinase-resistant penicillins (PRPs) react this way because of the activity of their beta-lactamase on these antimicrobial agents. These strains produced large amounts of staphylococcal beta-lactamase that rapidly hydrolyzed penicillin and partially hydrolyzed the PRPs. Susceptibility to hydrolysis was penicillin greater than oxacillin greater than cephalothin greater than methicillin. The borderline results and the hydrolysis could be prevented by the beta-lactamase inhibitors clavulanic acid and sulbactam. For intrinsically methicillin-resistant (heteroresistant) S. aureus, the inhibitors reduced the penicillin MICs, but the strains remained resistant to all the beta-lactam antimicrobial agents, including penicillin. We conclude that the borderline in vitro susceptibility or resistance to PRPs in most of these S. aureus strains is mediated by beta-lactamase and they are not heteroresistant or intrinsically resistant. We do not know whether this in vitro resistance is expressed clinically. PMID:3011847

Randomized, single-blind evaluation of cefadroxil and phenoxymethyl penicillin in the treatment of streptococcal pharyngitis.

PubMed Central

Pichichero, M E; Disney, F A; Aronovitz, G H; Talpey, W B; Green, J L; Francis, A B

1987-01-01

A total of 150 children from two pediatric practices with clinical and bacteriologic evidence of acute group A beta-hemolytic streptococcal (GABHS) pharyngitis randomly received cefadroxil monohydrate (75 children) or phenoxymethyl penicillin (75 children). Cefadroxil was given once daily, while penicillin was given three times daily. The treatment groups were similar in age, sex, race, illness severity, and acute GABHS symptomatology. Throat cultures were routine 3 to 5 days after the start of therapy and 2 and 14 days after the end of therapy. The bacterial cure rates were 90% (62 of 69) for cefadroxil-treated patients and 76% (52 of 68) for penicillin-treated patients. This difference was significant (P less than 0.04). The clinical response was satisfactory in 91% of cefadroxil-treated patients and 89% of penicillin-treated patients. We conclude that once-daily cefadroxil is at least as effective as three-times-daily penicillin in producing bacteriologic eradication and clinical symptomatic improvement in children with GABHS pharyngitis. PMID:3113329

Erythromycin and penicillin resistance mechanisms among viridans group streptococci isolated from blood cultures of adult patients with underlying diseases.

PubMed

Ergin, Alper; Eser, Özgen Köseoğlu; Hasçelik, Gülşen

2011-04-01

The aim of the study was to evaluate the species distribution, antimicrobial susceptibility and erythromycin-penicillin resistance mechanisms of viridans streptococci (VGS) isolates from blood cultures of adult patients with underlying diseases. Fifty VGS blood culture isolates were screened for their antibiotic susceptibilities against penicillin G, erythromycin and tetracycline by E-test. Clindamycin, cefotaxime, chloramphenicol, levofloxacin, linezolid and vancomycin susceptibility were performed by broth microdilution method. Erythromycin and penicillin resistance genotypes, ermB and mefA/E, pbp1a, pbp2b and pbp2x are amplified using PCR method. The clinical isolates included Streptococcus mitis (n. 19), S.oralis (n. 13), S.sanguinis, S.parasanguinis (n. 6, each), S.salivarius, S.vestibularis (n. 2, each), S.constellatus, S.sobrinus (n. 1, each). The percentage resistance against erythromycin and penicillin was 36% and 30%, respectively. The genotypic carriage rate of erythromycin resistance genes were: 56% ermB, 28% mefE, 8% ermB+mefE. Penicillin-resistant isolates carried pbp2b (33.3%) and pbp2x (20%) genes. Twenty-four VGS isolates were recovered from patients with cancer. S.mitis and S.oralis predominated among patients with cancer who had erythromycin and penicillin resistance isolates. The importance of classical antimicrobial agents like penicillin and erythromycin warrants the continuous surveillance of invasive VGS isolates and can guide better treatment options especially in patients with underlying diseases.

Daily penicillin serum concentrations following injection of 1.2 mega-units of ”all-purpose” penicillin

PubMed Central

Tinkler, A. E.; Hedges, A. J.; Shannon, R.

1965-01-01

In view of evidence suggesting that 1.2 mega-units of ”all-purpose” penicillin (300 000 IU potassium penicillin G, 300 000 IU procaine penicillin G and 600 000 IU benzathine penicillin) did not maintain treponemicidal serum concentrations during the week following injection—which if true, might necessitate a reappraisal of prophylactic and treatment schedules in wide use against syphilis—daily assays were performed to determine the penicillinaemia levels in ambulant adult males for one week following intramuscular injection with this dosage of two ”all-purpose” products (168 assays in all, 24 each day). Statistical evaluation of the results showed that the mean daily serum concentrations were, in fact, treponemicidal during the whole week after injection. The means of groups of 24 assays fell within narrow daily ranges on each of the seven post-injection days, suggesting that the long-acting component (benzathine penicillin) gives reliable and predictable daily levels in a high proportion of cases. This is in contrast to those penicillins which rely for their long-acting property on the oily gel in which they are suspended. On the other hand, the extremes of penicillinaemia for any individual in a large group were shown to cover a very wide range, demonstrating that a particular patient's failure to respond to standard treatment or prophylaxis can be due to factors quite unrelated to the quality or specificity of the product or to the sensitivity of the organism causing disease. PMID:5294592

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

PubMed

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.

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

PubMed

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; P<.001), whereas women whose reaction was not documented were less likely to receive cefazolin (18 [24.7%] compared with 63 [68.5%], respectively; P<.001). Among neonates whose mothers received appropriate compared with inappropriate antibiotics, there were no differences in Apgar score, number of blood draws, antibiotic use, length of hospital stay, or composite morbidity. More than half of women allergic to penicillin without anaphylaxis received an antibiotic other than penicillin or cefazolin as prophylaxis, indicating poor adherence to national guidelines.

21 CFR 558.155 - Chlortetracycline, sulfathiazole, penicillin.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline hydrochloride, 4.4 percent (20 grams) sulfathiazole, and procaine penicillin equivalent to 10 grams of penicillin per pound to No. 046573 in § 510.600(c) of this chapter. (2) 40 grams of chlortetracycline hydrochloride, 8.8...

21 CFR 558.155 - Chlortetracycline, sulfathiazole, penicillin.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline hydrochloride, 4.4 percent (20 grams) sulfathiazole, and procaine penicillin equivalent to 10 grams of penicillin per pound to No. 046573 in § 510.600(c) of this chapter. (2) 40 grams of chlortetracycline hydrochloride, 8.8...

21 CFR 558.155 - Chlortetracycline, sulfathiazole, penicillin.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline hydrochloride, 4.4 percent (20 grams) sulfathiazole, and procaine penicillin equivalent to 10 grams of penicillin per pound to No. 046573 in § 510.600(c) of this chapter. (2) 40 grams of chlortetracycline hydrochloride, 8.8...

21 CFR 558.155 - Chlortetracycline, sulfathiazole, penicillin.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline hydrochloride, 4.4 percent (20 grams) sulfathiazole, and procaine penicillin equivalent to 10 grams of penicillin per pound to No. 046573 in § 510.600(c) of this chapter. (2) 40 grams of chlortetracycline hydrochloride, 8.8...

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

Code of Federal Regulations, 2014 CFR

2014-04-01

..., and sulfamethazine. (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline per pound, 4.4 percent (20 grams) of sulfamethazine, and procaine penicillin equivalent in activity to 10 grams of penicillin per pound to 054771 in § 510.600(c) of this chapter. (2) 40 grams of...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

..., and sulfamethazine. (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline per pound, 4.4 percent (20 grams) of sulfamethazine, and procaine penicillin equivalent in activity to 10 grams of penicillin per pound to 046573 in § 510.600(c) of this chapter. (2) 40 grams of...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

..., and sulfamethazine. (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline per pound, 4.4 percent (20 grams) of sulfamethazine, and procaine penicillin equivalent in activity to 10 grams of penicillin per pound to 046573 in § 510.600(c) of this chapter. (2) 40 grams of...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

..., and sulfamethazine. (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline per pound, 4.4 percent (20 grams) of sulfamethazine, and procaine penicillin equivalent in activity to 10 grams of penicillin per pound to 046573 in § 510.600(c) of this chapter. (2) 40 grams of...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

..., and sulfamethazine. (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline per pound, 4.4 percent (20 grams) of sulfamethazine, and procaine penicillin equivalent in activity to 10 grams of penicillin per pound to 046573 in § 510.600(c) of this chapter. (2) 40 grams of...

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

PubMed

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.

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

USDA-ARS?s Scientific Manuscript database

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...

9 CFR 114.10 - Antibiotics as preservatives.

Code of Federal Regulations, 2012 CFR

2012-01-01

... restricted to: Amphotericin B 2.5 mcg. Nystatin (Mycostatin) 30.0 units Tetracyclines 30.0 mcg. Penicillin 30...) Permitted combinations: (1) Penicillin and streptomycin. (2) Either amphotericin B or nystatin, but not both... combination of penicillin and streptomycin, or with a combination of polymyxin B and neomycin. (3) The maximum...

Depletion of penicillin G residues in sows after intramuscular injection

USDA-ARS?s Scientific Manuscript database

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...

78 FR 59308 - Antimicrobial Animal Drug Sales and Distribution Annual Summary Report Data Tables

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

.... Antimicrobials which were reported in International Units (IU) (e.g., Penicillins) were converted to kg... ingredient. Antimicrobials which were reported in International Units (IU) (e.g., Penicillins) were converted.... Antimicrobials which were reported in International Units (IU) (e.g., Penicillins) were converted to kg...

9 CFR 114.10 - Antibiotics as preservatives.

Code of Federal Regulations, 2011 CFR

2011-01-01

... restricted to: Amphotericin B 2.5 mcg. Nystatin (Mycostatin) 30.0 units Tetracyclines 30.0 mcg. Penicillin 30...) Permitted combinations: (1) Penicillin and streptomycin. (2) Either amphotericin B or nystatin, but not both... combination of penicillin and streptomycin, or with a combination of polymyxin B and neomycin. (3) The maximum...

9 CFR 114.10 - Antibiotics as preservatives.

Code of Federal Regulations, 2014 CFR

2014-01-01

... restricted to: Amphotericin B 2.5 mcg. Nystatin (Mycostatin) 30.0 units Tetracyclines 30.0 mcg. Penicillin 30...) Permitted combinations: (1) Penicillin and streptomycin. (2) Either amphotericin B or nystatin, but not both... combination of penicillin and streptomycin, or with a combination of polymyxin B and neomycin. (3) The maximum...

21 CFR 522.1696 - Penicillin G procaine injectable dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin G procaine injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1696 Penicillin G procaine injectable dosage forms. ...

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

ERIC Educational Resources Information Center

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 CFR 114.10 - Antibiotics as preservatives.

Code of Federal Regulations, 2010 CFR

2010-01-01

... restricted to: Amphotericin B 2.5 mcg. Nystatin (Mycostatin) 30.0 units Tetracyclines 30.0 mcg. Penicillin 30...) Permitted combinations: (1) Penicillin and streptomycin. (2) Either amphotericin B or nystatin, but not both... combination of penicillin and streptomycin, or with a combination of polymyxin B and neomycin. (3) The maximum...

9 CFR 114.10 - Antibiotics as preservatives.

Code of Federal Regulations, 2013 CFR

2013-01-01

... restricted to: Amphotericin B 2.5 mcg. Nystatin (Mycostatin) 30.0 units Tetracyclines 30.0 mcg. Penicillin 30...) Permitted combinations: (1) Penicillin and streptomycin. (2) Either amphotericin B or nystatin, but not both... combination of penicillin and streptomycin, or with a combination of polymyxin B and neomycin. (3) The maximum...

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Code of Federal Regulations, 2010 CFR

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...

The Molecular Structure of Penicillin

NASA Astrophysics Data System (ADS)

Bentley, Ronald

2004-10-01

The chemical structure of penicillin was determined between 1942 and 1945 under conditions of secrecy established by the U.S. and U.K. governments. The evidence was not published in the open literature but as a monograph. This complex volume does not present a structure proof that can be readily comprehended by a student. In this article, a basic structural proof for the penicillin molecule is provided, emphasizing the chemical work. The stereochemistry of penicillin is also described, and various rearrangements are considered on the basis of the accepted β-lactam structure.

Diagnosis of penicillin allergy by skin testing: the Manitoba experience.

PubMed Central

Warrington, R. J.; Simons, F. E.; Ho, H. W.; Gorski, B. A.

1978-01-01

The reliability of skin testing in the diagnosis of penicillin allergy was studied in 86 adults and 167 children with a history of possible hypersensitivity reactions to penicillin. Skin testing was done with the major antigenic determinant of benzylpenicillin and minor determinants of benzylpenicillin, ampicillin, cloxacillin, methicillin and cephalothin. The overall frequency of positive skin reactions was 11.5%. Among the patients with positive skin reactions about half had a history of immediate or accelerated reactions to penicillins, but 2 of 11 adults and 50% of the children in this group had a history of maculopapular rash of delayed onset. There was a low frequency of positive skin reactions when there was a long interval between the times of clinical reaction and skin testing. Of 169 patients reacting negatively to skin testing who received a specific drug challenge only 2 manifested mild urticaria; this indicates the reliability of the skin tests in predicting penicillin allergy. The major and minor determinants of benzylpenicillin were the most useful reagents. One fifth of the patients with penicillin hypersensitivity would have been missed if the major determinant of benzylpenicillin alone had been used for skin testing. The additional use of the minor determinants of other penicillin derivatives, however, did not increase substantially the clinical reliability of the skin testing procedure. PMID:638909

Beta-lactam hypersensitivity and cross-reactivity.

PubMed

Terico, Adrienne T; Gallagher, Jason C

2014-12-01

Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are <5% and <1%, respectively. Similarities in penicillin and cephalosporin side chains may play a role in cross-reactivity between these classes. Cross-reactivity with monobactams is essentially negligible; however, there are some clinical data to support an interaction between ceftazidime and aztreonam, due to the similarity of their side chains. The data reviewed suggest that avoidance of other beta-lactams in patients with type 1 hypersensitivity to penicillins should be reconsidered. © The Author(s) 2014.

Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins.

PubMed

Gaeta, Francesco; Valluzzi, Rocco Luigi; Alonzi, Cristiana; Maggioletti, Michela; Caruso, Cristiano; Romano, Antonino

2015-04-01

Studies performed on samples larger than 100 subjects with a documented IgE-mediated hypersensitivity to penicillins have demonstrated a cross-reactivity rate of approximately 1% between penicillins and both imipenem and meropenem, whereas a single study found a cross-reactivity rate of 6.2% with aztreonam in 16 such subjects. To assess the cross-reactivity and tolerability of aztreonam and 3 carbapenems (imipenem-cilastatin, meropenem, and ertapenem) in patients with documented IgE-mediated hypersensitivity to penicillins. A total of 212 consecutive subjects with immediate reactions to penicillins and positive results on skin tests to at least 1 penicillin reagent underwent skin tests with aztreonam and carbapenems; subjects with negative results were challenged with escalating doses of aztreonam and carbapenems. All subjects displayed negative skin test results to both aztreonam and carbapenems; 211 accepted challenges and tolerated them. Challenges were not followed by full therapeutic courses. These data indicate the tolerability of both aztreonam and carbapenems in penicillin-allergic subjects. In those who especially require these alternative β-lactams, however, we recommend pretreatment skin tests, both because rare cases of cross-reactivity have been reported and because negative results indicate tolerability. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

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

PubMed

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 < .001), and the proportion of patients who could recall the name of the culprit drug was higher (P = .009) in the allergic group. Furthermore, histories of anaphylaxis (33.3%), urticaria, and/or angioedema (58.3%) were more common in the allergic group. Unspecified rashes (35.0%) and nonspecific symptoms (28.3%) predominated in the nonallergic group. Only 28.6% of patients with self-reported 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.

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

PubMed

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.

A Proactive Approach to Penicillin Allergy Testing in Hospitalized Patients.

PubMed

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.

Comparison of the effect of penicillins versus erythromycin in preventing neonatal group B streptococcus infection in active carriers following preterm prelabor rupture of membranes.

PubMed

Yeung, Sik Wing; Sahota, Daljit Singh; Leung, Tak Yeung

2014-06-01

To compare the incidence of neonatal group B streptococcus (GBS) infection in active GBS carriers with preterm prelabor rupture of membranes (PPROMs) after penicillins and erythromycin prophylaxis. Patients diagnosed to have PPROM between 2004 and 2009 inclusive were treated using erythromycin (erythromycin group), ampicillin, amoxicillin or co-amoxiclav (penicillin group), or no antibiotics (control group) according to department protocols depending on their gestation and their GBS status at the time of presentation. Patients receiving both erythromycin and penicillins were included in the penicillin group. The incidence of neonatal GBS infection was compared between groups categorized according to the antibiotic regime received. A total of 680 women were diagnosed to have PPROM of which 85 (12.5%) were active GBS carriers. GBS isolates were 100% sensitive to penicillins but only 35% were sensitive to erythromycin. There were 16, 22, and 47 patients in the penicillin, erythromycin, and control groups, respectively. The incidence of neonatal GBS infection in the three groups was 0%, 36%, and 13%, respectively, and was statistically significant (p = 0.023). Penicillins are more effective than erythromycin in preventing neonatal GBS infection in women with PPROM who were active GBS carriers. Because most women do not know their GBS status at the time of PPROM and it is practically difficult to identify the active carriers before delivery, ampicillin/amoxicillin should be used as a prophylactic antibiotic for active GBS carriers and women with unknown GBS carriage status to prevent neonatal GBS infection following PPROM. Copyright © 2014. Published by Elsevier B.V.

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

Code of Federal Regulations, 2010 CFR

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. ...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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. ...

78 FR 52536 - Withdrawal of Approval of New Animal Drug Applications; Diethylcarbamazine; Nicarbazin...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-23

...] Withdrawal of Approval of New Animal Drug Applications; Diethylcarbamazine; Nicarbazin; Penicillin; Roxarsone..., penicillin, and roxarsone in 3-way, combination drug Type C medicated feeds for broiler chickens and NADA 098-374 for use of nicarbazin and penicillin in 2-way, combination drug Type C medicated feeds for broiler...

21 CFR 520.1696 - Penicillin oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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. ...

21 CFR 520.1696 - Penicillin oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 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. ...

Correlation Between Growth Inhibition and the Binding of Various Penicillins and Cephalosporins to Staphylococcus aureus

PubMed Central

Edwards, John R.; Park, James T.

1969-01-01

The concentration of penicillin (or cephalosporin) required to achieve a given rate of binding to Staphylococcus aureus H correlates well with that required for inhibition of growth. This result suggests that the irreversible binding of penicillins and cephalosporins to cells is responsible for their biological activity. PMID:5808073

21 CFR 520.1696 - Penicillin oral dosage forms.

Code of Federal Regulations, 2010 CFR

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...

Characterization of Antibiotic-Loaded Alginate-Osa Starch Microbeads Produced by Ionotropic Pregelation

PubMed Central

Fontes, Gizele Cardoso; Calado, Verônica Maria Araújo; Rossi, Alexandre Malta; da Rocha-Leão, Maria Helena Miguez

2013-01-01

The aim of this study was to characterize the penicillin-loaded microbeads composed of alginate and octenyl succinic anhydride (OSA) starch prepared by ionotropic pregelation with calcium chloride and to evaluate their in vitro drug delivery profile. The beads were characterized by size, scanning electron microscopy (SEM), zeta potential, swelling behavior, and degree of erosion. Also, the possible interaction between penicillin and biopolymers was investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), and Fourier transform infrared (FTIR) analysis. The SEM micrograph results indicated a homogeneous drug distribution in the matrix. Also, based on thermal analyses (TGA/DSC), interactions were detected between microbead components. Although FTIR spectra of penicillin-loaded microbeads did not reveal the formation of new chemical entities, they confirmed the chemical drug stability. XRD patterns showed that the incorporated crystalline structure of penicillin did not significantly alter the primarily amorphous polymeric network. In addition, the results confirmed a prolonged penicillin delivery system profile. These results imply that alginate and OSA starch beads can be used as a suitable controlled-release carrier for penicillin. PMID:23862146

A programme to increase appropriate usage of benzathine penicillin for management of streptococcal pharyngitis and rheumatic heart disease in Zambia.

PubMed

Long, Aidan; Lungu, Joyce Chipili; Machila, Elizabeth; Schwaninger, Sherri; Spector, Jonathan; Tadmor, Brigitta; Fishman, Mark; Mayosi, Bongani M; Musuku, John

Rheumatic heart disease is highly prevalent and associated with substantial morbidity and mortality in many resource-poor areas of the world, including sub-Saharan Africa. Primary and secondary prophylaxis with penicillin has been shown to significantly improve outcomes and is recognised to be the standard of care, with intra-muscular benzathine penicillin G recommended as the preferred agent by many technical experts. However, ensuring compliance with therapy has proven to be challenging. As part of a public-private partnership initiative in Zambia, we conducted an educational and access-to-medicine programme aimed at increasing appropriate use of benzathine penicillin for the prevention and management of rheumatic heart disease, according to national guidelines. The programme was informed early on by identification of potential barriers to the administration of injectable penicillin, which included concern by health workers about allergic events. We describe this programme and report initial signs of success, as indicated by increased use of benzathine penicillin. We propose that a similar approach may have benefits in rheumatic heart disease programmes in other endemic regions.

A programme to increase appropriate usage of benzathine penicillin for management of streptococcal pharyngitis and rheumatic heart disease in Zambia

PubMed Central

Long, Aidan; Lungu, Joyce Chipili; Machila, Elizabeth; Musuku, John; Schwaninger, Sherri; Spector, Jonathan; Tadmor, Brigitta; Fishman, Mark; Mayosi, Bongani M

2017-01-01

Summary Rheumatic heart disease is highly prevalent and associated with substantial morbidity and mortality in many resourcepoor areas of the world, including sub-Saharan Africa.Primary and secondary prophylaxis with penicillin has beenshown to significantly improve outcomes and is recognisedto be the standard of care, with intra-muscular benzathine penicillin G recommended as the preferred agent by many technical experts. However, ensuring compliance with therapyhas proven to be challenging. As part of a public–privatepartnership initiative in Zambia, we conducted an educationaland access-to-medicine programme aimed at increasing appropriate use of benzathine penicillin for the preventionand management of rheumatic heart disease, according tonational guidelines. The programme was informed early onby identification of potential barriers to the administration ofinjectable penicillin, which included concern by health workers about allergic events. We describe this programme andreport initial signs of success, as indicated by increased useof benzathine penicillin. We propose that a similar approach may have benefits in rheumatic heart disease programmes in other endemic regions. PMID:28906539

Antibiotic bonding to polytetrafluoroethylene with tridodecylmethylammonium chloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

John F. Fulton, Coccidioidomycosis, and Penicillin

PubMed Central

Tager, Morris

1976-01-01

When the late Dr. John F. Fulton contracted severe pulmonary coccidioidomycosis in January, 1942, a metastatic lesion posed the threat of further progression and fatal dissemination. The possibility that an untested and generally unavailable antibiotic, penicillin, might be of value in Fulton's illness led his physician, Dr. John Bumstead, to appeal directly to Fulton to obtain this antibiotic, but ostensibly for the benefit of another patient succumbing to hemolytic streptococcal infection. While of no value for Fulton, penicillin was highly successful in the treatment of his other patient and soon of a second one with staphylococcal sepsis and pneumonia. This penicillin, administered in March, 1942, was the first clinical trial of penicillin under the control of the Office of Scientific Research and Development. The unique contribution of Dr. Fulton and of his illness to this event is described. ImagesFIG. 1FIG. 2 PMID:793204

Effect of Protein Binding on the Activity of Penicillins in Combination with Gentamicin Against Enterococci

PubMed Central

Glew, Richard H.; Moellering, Robert C.

1979-01-01

To assess the effect of protein binding by human serum on the synergistic interaction of penicillins with gentamicin, time-kill curves were determined for four penicillins alone and in combination with gentamicin against 10 blood isolates of enterococci. Killing curves demonstrated synergism with penicillin G plus gentamicin against all 10 strains in either broth or 50% human serum. In broth the combinations of nafcillin plus gentamicin and oxacillin plus gentamicin were synergistic against 10 of 10 strains and 4 of 10 strains, respectively. However, in serum, nafcillin plus gentamicin was synergistically bactericidal against only two strains and oxacillin plus gentamicin against none. Methicillin plus gentamicin was synergistic against none of the enterococci in either medium. Thus, the semisynthetic, penicillinase-resistant penicillins are unlikely to be effective in the therapy of patients with enterococcal endocarditis. PMID:426508

Radiation-induced polymerization for the immobilization of penicillin acylase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boccu, E.; Carenza, M.; Lora, S.

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 ofmore » the free-enzyme form, thus suggesting that penicillin acylase was entrapped in its native state into aqueous free spaces of the polymer matrix.« less

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

NASA Astrophysics Data System (ADS)

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.

Prediction of penicillin resistance in Staphylococcus aureus isolates from dairy cows with mastitis, based on prior test results.

PubMed

Grinberg, A; Lopez-Villalobos, N; Lawrence, K; Nulsen, M

2005-10-01

To gauge how well prior laboratory test results predict in vitro penicillin resistance of Staphylococcus aureus isolates from dairy cows with mastitis. Population-based data on the farm of origin (n=79), genotype based on pulsed-field gel electrophoresis (PFGE) results, and the penicillin-resistance status of Staph. aureus isolates (n=115) from milk samples collected from dairy cows with mastitis submitted to two diagnostic laboratories over a 6-month period were used. Data were mined stochastically using the all-possible-pairs method, binomial modelling and bootstrap simulation, to test whether prior test results enhance the accuracy of prediction of penicillin resistance on farms. Of all Staph. aureus isolates tested, 38% were penicillin resistant. A significant aggregation of penicillin-resistance status was evident within farms. The probability of random pairs of isolates from the same farm having the same penicillin-resistance status was 76%, compared with 53% for random pairings of samples across all farms. Thus, the resistance status of randomly selected isolates was 1.43 times more likely to correctly predict the status of other isolates from the same farm than the random population pairwise concordance probability (p=0.011). This effect was likely due to the clonal relationship of isolates within farms, as the predictive fraction attributable to prior test results was close to nil when the effect of within-farm clonal infections was withdrawn from the model. Knowledge of the penicillin-resistance status of a prior Staph. aureus isolate significantly enhanced the predictive capability of other isolates from the same farm. In the time and space frame of this study, clinicians using previous information from a farm would have more accurately predicted the penicillin-resistance status of an isolate than they would by chance alone on farms infected with clonal Staph. aureus isolates, but not on farms infected with highly genetically heterogeneous bacterial strains.

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

PubMed

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.

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

PubMed

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 created a new antibiotics industry and that opened the way for the establishment of over 100 industrial processes with immobilized biocatalysts worldwide today.

Rapid Detection of Penicillin-Resistant Streptococcus pneumoniae in Cerebrospinal Fluid by a Seminested-PCR Strategy

PubMed Central

du Plessis, Mignon; Smith, Anthony M.; Klugman, Keith P.

1998-01-01

A seminested-PCR assay, based on the amplification of the pneumococcal penicillin-binding protein 2B gene (pbp2B), was developed for the detection of penicillin-resistant and -susceptible pneumococci in cerebrospinal fluid (CSF) specimens. Species-specific primers (P5 and P6) which amplified a 682-bp conserved region of the transpeptidase-encoding region of the pbp2B gene were used. Four “resistance” primers were designed to bind to altered areas of the pbp2B gene identified in penicillin-resistant South African wild-type strains. Together with the downstream primer P6, the upstream resistance primers amplified fragments which were used to detect the presence of penicillin resistance. This system identified all 35 of the S. pneumoniae isolates evaluated, including strains of 11 different serotypes and a range of penicillin-resistant and -susceptible strains. The specificity of the assay was demonstrated by its inability to amplify DNA from other bacterial species which commonly cause meningitis. It was possible to detect pneumococcal DNA from culture-negative CSF inoculated with 2.5 pg of purified DNA or 18 CFU. Analysis of 285 CSF specimens showed that PCR detected the pneumococcus in 18 samples positive by culture, including the identification of four penicillin-resistant isolates. The positive predictive value and the negative predictive value of the assay were each 100%. PMID:9466757

Important Mutations Contributing to High-Level Penicillin Resistance in Taiwan19F-14, Taiwan23F-15, and Spain23F-1 of Streptococcus pneumoniae Isolated from Taiwan.

PubMed

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.

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

PubMed

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.

21 CFR 558.680 - Zoalene.

Code of Federal Regulations, 2013 CFR

2013-04-01

... subtable in item (i). Arsanilic acid 90 (0.01%) plus penicillin 2.4 to 50. Replacement chickens; growth... procaine penicillin; grower ration not to be fed to birds over 14 weeks of age; withdraw 5 d before...). Grower ration not to be fed to birds over 14 weeks of age; feed as in subtable in item (i). Penicillin 2...

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

USDA-ARS?s Scientific Manuscript database

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...

21 CFR 558.680 - Zoalene.

Code of Federal Regulations, 2010 CFR

2010-04-01

... subtable in item (i). Arsanilic acid 90 (0.01%) plus penicillin 2.4 to 50. Replacement chickens; growth... procaine penicillin; grower ration not to be fed to birds over 14 weeks of age; withdraw 5 d before...). Grower ration not to be fed to birds over 14 weeks of age; feed as in subtable in item (i). Penicillin 2...

21 CFR 558.680 - Zoalene.

Code of Federal Regulations, 2012 CFR

2012-04-01

... subtable in item (i). Arsanilic acid 90 (0.01%) plus penicillin 2.4 to 50. Replacement chickens; growth... procaine penicillin; grower ration not to be fed to birds over 14 weeks of age; withdraw 5 d before...). Grower ration not to be fed to birds over 14 weeks of age; feed as in subtable in item (i). Penicillin 2...

21 CFR 558.680 - Zoalene.

Code of Federal Regulations, 2011 CFR

2011-04-01

... subtable in item (i). Arsanilic acid 90 (0.01%) plus penicillin 2.4 to 50. Replacement chickens; growth... procaine penicillin; grower ration not to be fed to birds over 14 weeks of age; withdraw 5 d before...). Grower ration not to be fed to birds over 14 weeks of age; feed as in subtable in item (i). Penicillin 2...

Combined Effects of Hyperbaric Oxygen and Antimicrobials in a Model of Gas Gangrene.

DTIC Science & Technology

1992-06-30

mice. Immediately following bacterial inoculation, penicillin, imipenem , clindamycin or metronidazole were administered via, intraperitoneal injection...Mice treated with clindamycin or metronidazole survived significantly longer- than mice treated with penicillin G or imipenem (P - 0.05). HBO alone did...Immediately following bacterial inoculation, penicillin, imipenem , clindamycin or metronidazole were administered via intraperitoneal injection. HBO

Interspecies Mixed-Effect Pharmacokinetic Modeling of Penicillin G in Cattle and Swine

PubMed Central

Li, Mengjie; Gehring, Ronette; Tell, Lisa; Baynes, Ronald; Huang, Qingbiao

2014-01-01

Extralabel drug use of penicillin G in food-producing animals may cause an excess of residues in tissue which will have the potential to damage human health. Of all the antibiotics, penicillin G may have the greatest potential for producing allergic responses to the consumer of food animal products. There are, however, no population pharmacokinetic studies of penicillin G for food animals. The objective of this study was to develop a population pharmacokinetic model to describe the time-concentration data profile of penicillin G across two species. Data were collected from previously published pharmacokinetic studies in which several formulations of penicillin G were administered to diverse populations of cattle and swine. Liver, kidney, and muscle residue data were also used in this study. Compartmental models with first-order absorption and elimination were fit to plasma and tissue concentrations using a nonlinear mixed-effect modeling approach. A 3-compartment model with extra tissue compartments was selected to describe the pharmacokinetics of penicillin G. Typical population parameter estimates (interindividual variability) were central volumes of distribution of 3.45 liters (12%) and 3.05 liters (8.8%) and central clearance of 105 liters/h (32%) and 16.9 liters/h (14%) for cattle and swine, respectively, with peripheral clearance of 24.8 liters/h (13%) and 9.65 liters/h (23%) for cattle and 13.7 liters/h (85%) and 0.52 liters/h (40%) for swine. Body weight and age were the covariates in the final pharmacokinetic models. This study established a robust model of penicillin for a large and diverse population of food-producing animals which could be applied to other antibiotics and species in future analyses. PMID:24867969

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

PubMed

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.

Cross-Reactivity among Beta-Lactams.

PubMed

Romano, Antonino; Gaeta, Francesco; Arribas Poves, Maria Francisca; Valluzzi, Rocco Luigi

2016-03-01

Penicillins and cephalosporins are the major classes of beta-lactam (BL) antibiotics in use today and one of the most frequent causes of hypersensitivity reactions to drugs. Monobactams, carbapenems, oxacephems, and beta-lactamase inhibitors constitute the four minor classes of BLs. This review takes into account mainly the prospective studies which evaluated cross-reactivity among BLs in subjects with a well-demonstrated hypersensitivity to a certain class of BLs by performing allergy tests with alternative BLs and, in case of negative results, administering them. In subjects with either IgE-mediated or T-cell-mediated hypersensitivity, cross-reactivity among BLs, particularly among penicillins and among cephalosporins, as well as between penicillins and cephalosporins, seems to be mainly related to structural similarities among their side-chain determinants. Specifically, in penicillin-allergic subjects, cross-reactivity between penicillins and cephalosporins may exceed 30% when they are administered cephalosporins with identical side chains to those of responsible penicillins. In these subjects, a few prospective studies have demonstrated a rate of cross-reactivity between penicillins and both carbapenems and aztreonam lower than 1%. With regard to subjects with an IgE-mediated hypersensitivity to cephalosporins, in a single study, about 25% of the 98 subjects with such hypersensitivity had positive results to penicillins, 3% to aztreonam, 2% to imipenem/cilastatin, and 1% to meropenem. The cross-reactivity related to the selective recognition of the BL ring by IgE or T lymphocytes, which entails positive responses to all BLs tested, appears to be exceptional. Some studies concerning cross-reactivity among BLs have found patterns of allergy-test positivity which cannot be explained by either the common BL ring or by similar or identical side chains, thus indicating the possibility of coexisting sensitivities to different BLs because of prior exposures to them.

Prospective assessment of diagnostic tests for pediatric penicillin allergy, from clinical history to challenge tests✰,✰✰,✰✰✰.

PubMed

Ibáñez, María Dolores; Del Río, Pablo Rodríguez; Lasa, Eva Maria; Joral, Alejandro; Ruiz-Hornillos, Javier; Muñoz, Candelaria; Traseira, Carmen Gómez; Escudero, Carmelo; Olaguibel Rivera, Jose María; Garriga-Baraut, Teresa; González-de-Olano, David; Rosado, Ana; Sanchez-García, Silvia; Bustamante, Socorro Pérez; Vilchez, Maria Antonia Padial; Montaño, Patricia Prieto; Morillo, Rocío Candón; Iglesia, Eva Macías; Vila, Angélica Feliú; Valbuena, Teresa; Lopez-Patiño, Ana; Martorell, Antonio; Sastre, Joaquín; Audícana, María Teresa

2018-05-24

Diagnostic guidelines for penicillin allergy in children recommend cumbersome protocols based partially on data from adults, which may be suboptimal for pediatric use. To assess the accuracy of tools for diagnosis of penicillin allergy in children. A prospective multicenter study was conducted in children with reported adverse events related to penicillin, excluding severe reactions. All patients underwent a uniform diagnostic protocol consisting of clinical history, skin tests, serum specific IgE, and, regardless of these results, drug provocation tests (DPT). 732 children (mean 5.5 years; 51.2% males) completed the allergy work-up, including DPT. Amoxicillin triggered 96.9% of all reactions. None of the patients with an immediate index reaction (IR) developed a reaction on DPT. Penicillin allergy was confirmed in 35 subjects (4.8%): 6(17%) immediate and 29(83%) non-immediate reactions in the DPT. No severe reactions were recorded. The allergist diagnosis based upon the clinical history was not associated with the final outcome at DPT. In 30 of 33(91%) allergic patients, all skin tests and sIgE were negative. A logistic regression model identified the following to be associated with PNC allergy (p<0.05): a family history of drug allergy (OR=3.03; 95% confidence interval (CI): 1.33-6.89), an IR lasting >3 days vs ≤24 hours (OR=8.96; 95% CI: 2.01-39.86), and IR while receiving corticosteroids (OR=2.68; 95% CI: 1.30-5.54). Conventional predictors of allergy to penicillin performed weakly. The authors propose straightforward penicillin provocation testing in controlled, experienced centers for the diagnosis of non-severe penicillin allergy in children. Copyright © 2018. Published by Elsevier Inc.

Testing of Streptococcus pneumoniae for resistance to penicillin.

PubMed Central

Marshall, K J; Musher, D M; Watson, D; Mason, E O

1993-01-01

The increasing prevalence of penicillin-resistant Streptococcus pneumoniae requires antibiotic susceptibility tests that can be done with greater ease and reliability. We measured the MIC of penicillin for pneumococci by the tube macrodilution method with Mueller-Hinton broth (MHB), Haemophilus Test Medium (HTM), Todd-Hewitt broth with 0.5% yeast extract (THY), and MHB with 3% lysed horse blood (LHB). Eight (19%) and 6 (14%) of 42 pneumococcal isolates failed to generate turbid growth in MHB and HTM, respectively, whereas all pneumococcal isolates did so in THY and LHB. For those strains that replicated to turbidity, the mean MICs of penicillin were lower in MHB and HTM than in THY and LHB, with differences being significant (P < 0.05) for comparisons with LHB. Four isolates appeared to be penicillin susceptible in HTM but were actually moderately resistant in THY and LHB, and two isolates appeared to be moderately resistant but were resistant. A similar failure to detect resistance was seen with MHB. S. pneumoniae ATCC 49619, a moderately penicillin-resistant strain that has been proposed for quality control testing, gave variable results in MHB or THM and appeared to be susceptible to penicillin in some assays, whereas the MICs for S. pneumoniae ATCC 49619 in THY or LHB fell within a twofold dilution range, with geometric means of 0.16 and 0.18 micrograms/ml, respectively. Pneumococcal isolates thus may appear falsely susceptible to penicillin when tested in MHB or HTM. LHB remains the standard medium; however, because THY is an easily prepared clear medium that can be used in automated systems and appears to yield results similar to those obtained with LHB, THY deserves consideration for routine use. PMID:8501225

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

PubMed

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.

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.

PubMed

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 (P<0.001). In the former, penicillin 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.

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

PubMed

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.

A novel hybrid metal-organic framework-polymeric monolith for solid-phase microextraction.

PubMed

Lin, Chen-Lan; Lirio, Stephen; Chen, Ya-Ting; Lin, Chia-Her; Huang, Hsi-Ya

2014-03-17

This study describes the fabrication of a novel hybrid metal-organic framework- organic polymer (MOF-polymer) for use as a stationary phase in fritless solid-phase microextraction (SPME) for validating analytical methods. The MOF-polymer was prepared by using ethylene dimethacrylate (EDMA), butyl methacrylate (BMA), and an imidazolium-based ionic liquid as porogenic solvent followed by microwave-assisted polymerization with the addition of 25 % MOF. This novel hybrid MOF-polymer was used to extract penicillin (penicillin G, penicillin V, oxacillin, cloxacillin, nafcillin, dicloxacillin) under different conditions. Quantitative analysis of the extracted penicillin samples using the MOF-organic polymer for SPME was conducted by using capillary electrochromatography (CEC) coupled with UV analysis. The penicillin recovery was 63-96.2 % with high reproducibility, sensitivity, and reusability. The extraction time with the proposed fabricated SPME was only 34 min. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cross-over assessment of serum bactericidal activity of moxifloxacin and levofloxacin versus penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae in healthy volunteers.

PubMed

Hart, Daniel; Weinstein, Melvin P

2007-07-01

We compared the serum bactericidal activity (SBA) of moxifloxacin and levofloxacin against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae in 12 healthy volunteers. Each subject received 3 days of oral moxifloxacin 400 mg daily and levofloxacin 750 mg daily, respectively, with a 2- to 4-week washout period between regimens. Blood was drawn at 6 time points after the third dose of each antibiotic. Mean serum bactericidal titers (MSBTRs) for moxifloxacin were 4-fold higher than the mean titers for levofloxacin at each time point. For each drug, MSBTRs at each time point were the same or within one 2-fold dilution when analyzed according to the penicillin susceptibility of the strains or the sex of the subjects. The difference in SBA of the 2 drugs may have implications for the emergence of resistance and clinical outcome.

In Vitro Activity of Cephalothin and Three Penicillins Against Escherichia coli and Proteus Species

PubMed Central

Barry, Arthur L.; Hoeprich, Paul D.

1973-01-01

The susceptibility of clinical isolates of Escherichia coli (67) and Proteus species (58) to cephalothin, ampicillin, benzyl penicillin, and phenoxymethyl penicillin was determined in vitro by using broth dilution and disk diffusion tests. The data were correlated by using a four-category scheme for interpreting minimal inhibitory concentrations (groups 1 to 4) as recommended by a subcommittee of an international collaborative study of susceptibility testing. With cephalothin and ampicillin, groups 1 (susceptible) and 2 (moderately susceptible) were susceptible by the disk test, and with benzyl penicillin, similar results were observed when the interpretive zone standards were changed. Strains categorized as group 4 (very resistant) were resistant by the disk method, but group 3 (moderately resistant) strains were not adequately distinguished by disk testing. Group 3 susceptibility to benzyl and phenoxymethyl penicillins can be predicted by extrapolating results from tests with ampicillin disks. PMID:4202343

The Second International Standard for Penicillin*

PubMed Central

Humphrey, J. H.; Mussett, M. V.; Perry, W. L. M.

1953-01-01

In 1950 the Department of Biological Standards, National Institute for Medical Research, London, was authorized by the WHO Expert Committee on Biological Standardization to prepare the Second International Standard for Penicillin. A single batch of specially recrystallized sodium penicillin G was obtained and 11 laboratories in seven different countries were requested to take part in its collaborative assay. 112 assays were carried out, of which 101 were done by cup-plate methods using either Staphylococcus aureus or Bacillus subtilis. The results were subjected to standard methods of analysis, on the basis of which the authors define the Second International Standard for Penicillin as containing 1,670 International Units (IU) per mg, with limits of error (P = 0.05) of 1,666-1,674 IU/mg. The International Unit is therefore redefined as the activity contained in 0.0005988 mg of the Second International Standard for Penicillin. PMID:13082387

What do I need to know about penicillin antibiotics?

PubMed

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/.

Penicillin’s Discovery and Antibiotic Resistance: Lessons for the Future?

PubMed Central


Lobanovska, Mariya; Pilla, Giulia

2017-01-01

Undoubtedly, the discovery of penicillin is one of the greatest milestones in modern medicine. 2016 marks the 75th anniversary of the first systemic administration of penicillin in humans, and is therefore an occasion to reflect upon the extraordinary impact that penicillin has had on the lives of millions of people since. This perspective presents a historical account of the discovery of the wonder drug, describes the biological nature of penicillin, and considers lessons that can be learned from the golden era of antibiotic research, which took place between the 1940s and 1960s. Looking back at the history of penicillin might help us to relive this journey to find new treatments and antimicrobial agents. This is particularly relevant today as the emergence of multiple drug resistant bacteria poses a global threat, and joint efforts are needed to combat the rise and spread of resistance. PMID:28356901

Untoward penicillin reactions

PubMed Central

Guthe, T.; Idsöe, O.; Willcox, R. R.

1958-01-01

The literature on untoward reactions following the administration of penicillin is reviewed. These reactions, including a certain number of deaths which have been reported, are of particular interest to health administrations and to WHO in view of the large-scale programmes for controlling the treponematoses which are now under way—programmes affecting millions of people in many parts of the world. The most serious problems are anaphylactic sensitivity phenomena and superinfection or cross-infection with penicillin-resistant organisms, and the reactions involved range in intensity from the mildest to the fatal; the incidence of the latter is estimated at 0.1-0.3 per million injections. The authors point out that with increasing use of penicillin, more persons are likely to become sensitized and the number of reactions can therefore be expected to rise. The best prevention against such an increase is the restriction of the unnecessary use of penicillin. PMID:13596877

Cleveland Clinic Rehabilitation Research Program

DTIC Science & Technology

2015-12-01

Study 1: The penicillin-induced seizure animal model has been generated by acute focal intracortical injection of penicillin in the motor cortex of rats ... motor cortex of rats . The effects of transcranial magnetic stimulation (TMS) on penicillin-induced seizure have been investigated using behavioral...electroencephalographic (EEG) recording. Study 2: The motor cortex (M1) and the corticospinal tracts (CST) will be directly modulated using brain stimulation

Penicillin treatment for gonorrhoea in relation to early syphilis in prostitutes.

PubMed Central

Bradbeer, C S; Thin, R N; Tan, T; Thirumoorthy, T

1988-01-01

A retrospective study of prostitutes in Singapore showed that they had received less antigonorrhoeal treatment with penicillin derivatives during the three month period before early syphilis was diagnosed than in other three month periods when they had not developed syphilis. This suggests that penicillin derivatives in doses sufficient to treat gonorrhoea will abort coincidental early syphilis. PMID:3346033

Antimicrobial Activity of Penicillin G and N-acetylcystein on Planktonic and Sessile Cells of Streptococcus suis.

PubMed

Espinosa, Ivette; Báez, Michel; Lobo, Evelyn; Martínez, Siomara; Gottschalk, Marcelo

2016-01-01

The aim of this study was to investigate the capacity of Streptococcus suis strains to form biofilms and to evaluate the antimicrobial activity of Penicillin G and N-acetylcystein (NAC) on both S. suis sessile and planktonic forms. Only non-typeable isolates of S. suis were correlated with a greater biofilm formation capacity. The MCI of Penicillin G and NAC required for inhibiting biofilm growth were higher than the required concentration for inhibiting planktonic growth. The combinations of NAC and Penicillin G showed a strong synergistic activity that inhibited biofilm formation and disrupted the pre-formed biofilm of S. suis.

Focal stimulation of the brain by entirely extracranial means. An example of radiation controlled focal pharmacology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Remler, M.P.

A method for focal stimulation of the brain by entirely extracranial means is presented. A focal x ray lesion of cortex was made that reduces the blood-brain barrier in that area. Then parenteral penicillin was administered. Penicillin is primarily confined to the vascular space by the blood-brain barrier in all parts of the brain except for some leakage into the brain at higher doses. An increased concentration of penicillin is created in the irradiated cortex. The penicillin creates a focal epileptic lesion in the irradiated area. This is an example of radiation-controlled focal pharmacology in the central nervous system. (auth)

Studies on the effects of gamma radiation on 6-aminopenicillanic acid and its derivatives by the EPR method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dziegielewski, J.; Jezowska-Trzebiatowska, B.; Kozlowski, H.

Commercial samples of 6-aminopenicillanic acid (6-APA), potassium benzyl- penicillin; procaine benzyl-penicillin, procaine hydrochlorides and sodium 3-(o- chlorophenyl)-5-methyl-4-isoxasol penicillin salt were irradiated with 0.5 to 40 Mrad and examined by the EPR method within the temperature range 100 to 300 deg K. No influence of the irradiation dose on powder EPR spectra structure has been stated, except for benzyl-penicillin procaine. In irradiated samples of antibiotics the presence of radicals with unpaired electrons on sulfur atoms and carbon atoms abuttmg on the thioether group has been stated. (auth)

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

PubMed

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.

Treatment of gonorrhoea in males in the Central African Republic with spectinomycin and procaine penicillin

PubMed Central

Meheus, André; Widy-Wirski, Roslaw; D'Costa, Joye; Van Dyck, Eddy; Delgadillo, René; Piot, Peter

1984-01-01

Gonorrhoea has become a problem in most parts of the world, and valid recommendations for treatment are important for control of the disease. In this study in Bangui, Central African Republic, 460 male patients with gonorrhoea were randomly assigned to treatment with either 4.0 × 106 units of procaine penicillin plus 1 g of probenecid, or 2 g of spectinomycin. Of these patients, 91% returned for follow-up; the failure rate was 4.8% with the penicillin schedule and 6.2% with spectinomycin (difference not statistically significant). Concomitant Chlamydia trachomatis infection was found in 5% of patients, and almost all of this group developed postgonococcal urethritis. Of the 460 patients, 7 (1.5%) were infected with penicillinase-producing Neisseria gonorrhoeae (PPNG) strains. Penicillin treatment failed in these cases, while spectinomycin was highly efficacious. The failure rate for penicillin was considerably higher in infections with strains that were less sensitive to penicillin in vitro. The failure rate for spectinomycin treatment was higher in patients who were infected with a strain that was highly sensitive to penicillin. It is concluded that, once PPNG strains have been found in a country, treatment of gonorrhoea should be based on an antibiotic that cures PPNG infections. Tetracycline can be used as second-line treatment, since it will also cure C. trachomatis infection, which is much less frequently associated with gonorrhoea in Africa than in industrial countries. PMID:6232015

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

PubMed Central

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

1999-01-01

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

Penicillin dosing for pneumococcal pneumonia.

PubMed

Bryan, C S; Talwani, R; Stinson, M S

1997-12-01

Most textbook authors still endorse penicillin G as the specific antibiotic of choice for pneumococcal pneumonia. However, problems with early precise etiologic diagnosis of pneumonia and the emergence of drug-resistant pneumococci cause penicillin to be seldom used for this purpose today. A third explanation for the infrequent use of penicillin is lack of clear consensus dosing guidelines. Emergence of pneumococci resistant to the newer cephalosporins and concerns about overuse of vancomycin, however, have prompted renewed interest in the development of precise, rapid methods for diagnosis of pneumococcal pneumonia with the implication that penicillin might be used more frequently. We review several issues concerning penicillin dosing: intermittent vs continuous therapy, high dose vs low dose, relationship of dose to resistance, and cost-effective pharmacology. An optimum "high-dose" regimen for life-threatening pneumococcal pneumonia in a 70-kg adult consists of a 3 million unit (mu) loading dose followed by continuous infusion of 10 to 12 mu of freshly prepared drug every 12 h. The maintenance dose should be reduced in elderly patients and in patients with renal failure according to the following formula: dose (mu/24 h = 4+[creatinine clearance divided by 7]). This regimen provides a penicillin serum level of 16 to 20 microg/mL, which should suffice for all but the most highly resistant strains (minimum inhibitory concentration > or = 4 microg/mL). Newer cephalosporins and vancomycin can be reserved for patients with suspected meningitis or endocarditis or for localities in which highly resistant pneumococci are known to be prevalent.

Radioallergosorbent testing for penicillin allergy in family practice.

PubMed Central

Worrall, G J; Hull, C; Briffett, E

1994-01-01

OBJECTIVES: To determine (a) the prevalence of patients supposedly allergic to penicillin who have a positive radioallergosorbent test (RAST) result for penicillin G or V and (b) the predictive power of family physicians' clinical judgement that a patient who is supposedly allergic to penicillin will have a positive RAST result. DESIGN: Prospective multicentre cross-sectional observational study. SETTING: Eleven primary care practices in Newfoundland; 10 were in a rural setting. PATIENTS: Of 110 consecutive adult patients with a supposed allergy to penicillin 97 agreed to participate in the study; 92 underwent RAST. INTERVENTIONS: Patients helped physicians complete a questionnaire and had a venous blood sample taken for the RAST. Physicians examined the clinical history and judged whether the patient was likely to have a positive RAST result. MEAN OUTCOME MEASURES: Rates of positive and negative RAST results for penicillin V and G. RESULTS: Of the 92 patients 8 had a positive RAST result and 84 a negative one. The positive predictive power of a "good" clinical history (e.g., urticaria, swollen eyes, tongue or lips, or an anaphylactic reaction witnessed by a physician) was low (10%); the negative predictive power of a "poor" clinical history (e.g., nausea, vomiting, diarrhea, fever, nonspecific rash or fainting) was 92%. CONCLUSIONS: Less than 10% of primary care patients with a supposed allergy to penicillin will have a positive RAST result. In addition, physicians' predictions of allergy in such patients are imprecise. PMID:8275407

High frequency of fluoroquinolone- and macrolide-resistant streptococci among clinically isolated group B streptococci with reduced penicillin susceptibility.

PubMed

Kimura, Kouji; Nagano, Noriyuki; Nagano, Yukiko; Suzuki, Satowa; Wachino, Jun-ichi; Shibayama, Keigo; Arakawa, Yoshichika

2013-03-01

Recently several clinical isolates of Streptococcus agalactiae [also known as group B Streptococcus (GBS)] that have acquired reduced penicillin susceptibility (PRGBS) by amino acid substitutions in the penicillin-binding protein 2X have emerged. The frequency of fluoroquinolone (FQ)- and macrolide-resistant streptococci among PRGBS is not yet known. Fifty-seven GBS [19 PRGBS and 38 penicillin-susceptible GBS (PSGBS)], isolated from different medical institutions in Japan, were studied. For GBS, the MICs of penicillin G, levofloxacin and erythromycin were determined using the agar dilution method. Nineteen PRGBS were previously confirmed as genetically diverse streptococci by PFGE. Further, the mechanisms underlying penicillin, FQ and macrolide non-susceptibility/resistance were analysed. The frequency of non-susceptibility to FQs among PSGBS was 18.4% (7/38), whereas that among PRGBS was 100% (19/19). The frequency of resistance to erythromycin among PSGBS was 7.9% (3/38), while that among PRGBS was 47.4% (9/19). Statistical significance was determined using Fisher's exact test between reduced penicillin susceptibility and FQ non-susceptibility (P ≤ 0.0001) and macrolide resistance (P=0.0012). The resistance/non-susceptibility mechanisms among PRGBS were diverse, suggesting that the PRGBS examined were not clonal. PRGBS isolates tend to show resistance to FQs and/or macrolides. Because the drug choice for treating these multidrug-resistant GBS is more limited than that for usual GBS, these strains may present future public health challenges.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

Evaluation of Enterococcus faecalis clinical isolates with 'penicillin-resistant, ampicillin-susceptible' phenotype as reported by Vitek-2 Compact system.

PubMed

Tan, Yen Ee; Ng, Lily S Y; Tan, Thean Yen

2014-10-01

It has been recently reported that ampicillin susceptibility cannot accurately predict piperacillin and imipenem susceptibilities in penicillin-resistant, ampicillin-susceptible (Pen-R, Amp-S) Enterococcus faecalis isolates, contrary to the current Clinical and Laboratory Standards Institute (CLSI) recommendations. This has important therapeutic implications. Such isolates were noted after the use of Vitek-2 Compact system AST-GP67 susceptibility cards in a Singapore general hospital and they were increasing in numbers. The primary aim of this study was to evaluate these clinical isolates against microbroth dilution (MBD) technique and other commonly used antimicrobial susceptibility test (AST) methods for penicillin and ampicillin. The secondary aim was to evaluate whether ampicillin susceptibility could indeed be a reliable surrogate marker for piperacillin and imipenem susceptibilities in E. faecalis isolates that were confirmed Pen-R, Amp-S.From 2009 to 2013, a total of 49 isolates (5%) of 983 non-duplicate E. faecalis tested by Vitek-2 displayed the 'Pen-R, Amp-S' phenotype in a general hospital in Singapore. These were tested against MBD which was the reference method, Etest and disc diffusion for penicillin and ampicillin. Susceptibilities to piperacillin and imipenem were also tested using MBD. In addition, β-lactamase production test was performed. Forty E. faecalis isolates with penicillin-susceptible, ampicillin-susceptible (Pen-S, Amp-S) phenotype were included for comparative purposes.The categorical agreement rate was 100% for all AST methods in ampicillin reporting for the 'Pen-R, Amp-S' group of E. faecalis isolates. However, a large number of isolates (46 isolates, 93.9%) fell into the major error category for penicillin testing by the Vitek-2 system. Penicillin minimum inhibitory concentrations (MICs) generated by the Vitek-2 system for the majority of these isolates were two doubling dilutions higher compared to those obtained by the reference test. The Etest method correlated well with the MBD method. Thirty-two isolates (65.3%) were in categorical agreement with the MBD method when tested by the disc diffusion method for penicillin. Only three E. faecalis isolates (6.1%) were confirmed to have the uncommon penicillin resistance phenotype, with two of them showing resistance to piperacillin and intermediate to imipenem. β-lactamase production test was negative for all isolates. Among the Pen-S, Amp-S E. faecalis isolates, the categorical agreement was 100% for penicillin and ampicillin in all the tested methods.Enterococcus faecalis with 'Pen-R, Amp-S' phenotype reported by the Vitek-2 system using AST-GP67 susceptibility cards must be confirmed with a reference test, the Etest method being a good alternative. The Vitek-2 system generated higher penicillin MIC readings compared to MBD in this study. The actual prevalence of this uncommon penicillin resistance phenotype in E. faecalis was found to be low in this institution. More studies are required to confirm the reliability of ampicillin as a surrogate marker for piperacillin and imipenem susceptibilities in these isolates.

9 CFR 147.15 - Laboratory procedure recommended for the bacteriological examination of mycoplasma reactors. 12

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10523. (5) Use sterile deionized distilled water to reconstitute penicillin. (6) Sterile serum should be... samples (ml)—5.0 (1:2000) Mycoplasma Broth Base (g)—22.5 Aqueous penicillin (units)—500,000 Sterile serum... Aqueous penicillin (units)—400,000 NAD (ml)—12.5 Cysteine hydrochloride (ml)—12.5 (1) Rotate flask gently...

9 CFR 147.15 - Laboratory procedure recommended for the bacteriological examination of mycoplasma reactors. 12

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10523. (5) Use sterile deionized distilled water to reconstitute penicillin. (6) Sterile serum should be... samples (ml)—5.0 (1:2000) Mycoplasma Broth Base (g)—22.5 Aqueous penicillin (units)—500,000 Sterile serum... Aqueous penicillin (units)—400,000 NAD (ml)—12.5 Cysteine hydrochloride (ml)—12.5 (1) Rotate flask gently...

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

NASA Astrophysics Data System (ADS)

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.

9 CFR 147.15 - Laboratory procedure recommended for the bacteriological examination of mycoplasma reactors. 12

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10523. (5) Use sterile deionized distilled water to reconstitute penicillin. (6) Sterile serum should be... samples (ml)—5.0 (1:2000) Mycoplasma Broth Base (g)—22.5 Aqueous penicillin (units)—500,000 Sterile serum... Aqueous penicillin (units)—400,000 NAD (ml)—12.5 Cysteine hydrochloride (ml)—12.5 (1) Rotate flask gently...

Magnetic Stimulation and Epilepsy

DTIC Science & Technology

2013-10-14

the seizure-induced groups exhibited varying degrees of EEG activity reduction. Figure 2. The effects of TMS on penicillin-induced seizures...the EEG recording including (a) baseline (pre-penicillin injection), (b) 30-min post-penicillin injection (30min-PI), (c) 10-min post- TMS stimulation...stable conditions 55% faster, and the 5 pps TMS -treated group 78% faster. Figure 3. Maximum frequency relationships in EEG activity among the

Pharmacodynamic effects of amoxicillin versus cefotaxime against penicillin-susceptible and penicillin-resistant pneumococcal strains: a phase I study.

PubMed Central

Aguilar, L; Rosendo, J; Balcabao, I P; Martín, M; Giménez, M J; Frías, J; Prieto, J

1997-01-01

Serum bactericidal activity against a penicillin-susceptible strain and a penicillin-resistant strain of Streptococcus pneumoniae (amoxicillin and cefotaxime MICs, 0.001 and 1 microg/ml, respectively, and MBCs, 0.01 and 2 microg/ml, respectively) was measured in 12 healthy volunteers who each received an oral 875-mg dose of amoxicillin and an intramuscular 1-g dose of cefotaxime in a crossover fashion. The areas under the bactericidal activity-time curves for the two strains were found to be similar for both antibiotics despite the significantly higher (P < 0.002) AUC/MIC and peak level/MIC values for cefotaxime. PMID:9174206

Comparison of microbial growth inhibition screening assays with high-pressure liquid chromatography for detection of experimentally incurred penicillin G residues in calves.

PubMed

Musser, Jeffrey M B; Anderson, Kevin L; Boison, Joe O

2002-01-01

Twelve calves were fed milk replacer containing 3.33 ppm penicillin G for one feeding, and 12 calves were fed the medicated milk replacer once daily at a rate of 12% of their body weight for 14 days. Two calves served as controls. Calves were slaughtered 4 to 13 hours after being fed. Kidney, liver, muscle, and urine samples were assayed for penicillin by high-pressure liquid chromatography (HPLC). Penicillin G was not detected in any muscle samples and concentrations of penicillin exceeded the tolerance level (0.05 microg/g) in kidney or liver tissue from 13 of 24 treated-calf carcasses examined by HPLC. The Live Animal Swab Test identified all 13 carcasses with violative drug residues. Using kidney as the test matrix, the Swab Test on Premises identified 10 of 13 carcasses with violative drug residues, while the Calf Antibiotic Sulfa Test identified seven of 13 carcasses with violative residues.

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

PubMed

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.

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

PubMed

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.

Antibiotic Therapy of Staphylococcal Infections

PubMed Central

Hawks, Gordon H.

1965-01-01

The antibiotic treatment of staphylococcal infections remains a problem. Isolation of the organism and sensitivity testing are necessary in the choice of antibiotic. Penicillin G is the most effective penicillin against non-penicillinase-producing staphy-lococci; for the penicillinase producers there is very little to choose between the semisynthetic penicillins, methicillin, cloxacillin, nafcillin and oxacillin. For patients who are hypersensitive to penicillin, the bacteriostatic drugs (erythromycin, novobiocin, tetracycline, chloramphenicol, oleandomycin) are useful for mild infections, while for more severe illness the bactericidal drugs (vancomycin, ristocetin, kanamycin, bacitracin, neomycin) have been used successfully. Acute staphylococcal enterocolitis is probably best treated by a semisynthetic penicillin. Other antibiotics which have been found useful, with clinical trials, for staphylococcal infections are cephalosporin, fucidin, cephaloridine and lincomycin. The latter drug has been reported of value in the treatment of osteomyelitis. There is little justification for the prophylactic use of antibiotics to prevent staphylococcal infection. Surgical drainage is still an important adjunct in the treatment of many staphylococcal infections. PMID:5318575

Aggregated Antibiograms and Monitoring of Drug-Resistant Streptococcus pneumoniae

PubMed Central

Lexau, Catherine; Baughman, Wendy; Barnes, Brenda; Bennett, Nancy; Cassidy, P. Maureen; Pass, Margaret; Gelling, Lisa; Barrett, Nancy L.; Zell, Elizabeth R.; Whitney, Cynthia G.

2003-01-01

Community-specific antimicrobial susceptibility data may help monitor trends among drug-resistant Streptococcus pneumoniae and guide empiric therapy. Because active, population-based surveillance for invasive pneumococcal disease is accurate but resource intensive, we compared the proportion of penicillin-nonsusceptible isolates obtained from existing antibiograms, a less expensive system, to that obtained from 1 year of active surveillance for Georgia, Tennessee, California, Minnesota, Oregon, Maryland, Connecticut, and New York. For all sites, proportions of penicillin-nonsusceptible isolates from antibiograms were within 10 percentage points (median 3.65) of those from invasive-only isolates obtained through active surveillance. Only 23% of antibiograms distinguished between isolates intermediate and resistant to penicillin; 63% and 57% included susceptibility results for erythromycin and extended-spectrum cephalosporins, respectively. Aggregating existing hospital antibiograms is a simple and relatively accurate way to estimate local prevalence of penicillin-nonsusceptible pneumococcus; however, antibiograms offer limited data on isolates with intermediate and high-level penicillin resistance and isolates resistant to other agents. PMID:14519245

Purification and sequencing of the active site tryptic peptide from penicillin-binding protein 1b of Escherichia coli

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicholas, R.A.; Suzuki, H.; Hirota, Y.

This paper reports the sequence of the active site peptide of penicillin-binding protein 1b from Escherichia coli. Purified penicillin-binding protein 1b was labeled with (/sup 14/C)penicillin G, digested with trypsin, and partially purified by gel filtration. Upon further purification by high-pressure liquid chromatography, two radioactive peaks were observed, and the major peak, representing over 75% of the applied radioactivity, was submitted to amino acid analysis and sequencing. The sequence Ser-Ile-Gly-Ser-Leu-Ala-Lys was obtained. The active site nucleophile was identified by digesting the purified peptide with aminopeptidase M and separating the radioactive products on high-pressure liquid chromatography. Amino acid analysis confirmed thatmore » the serine residue in the middle of the sequence was covalently bonded to the (/sup 14/C)penicilloyl moiety. A comparison of this sequence to active site sequences of other penicillin-binding proteins and beta-lactamases is presented.« less

Using steric hindrance to design new inhibitors of class C beta-lactamases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trehan, Indi; Morandi, F.; Blaszczak, L.C.

{beta}-lactamases confer resistance to {beta}-lactam antibiotics such as penicillins and cephalosporins. However, {beta}-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of {beta}-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R1 side chain of {beta}-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective {beta}-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of themore » penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.« less

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

PubMed Central

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

Combined Real-Time PCR and Pyrosequencing Strategy for Objective, Sensitive, Specific, and High-Throughput Identification of Reduced Susceptibility to Penicillins in Neisseria meningitidis▿

PubMed Central

Thulin, Sara; Olcén, Per; Fredlund, Hans; Unemo, Magnus

2008-01-01

A segment of penA in Neisseria meningitidis strains (n = 127), including two nucleotide sites closely associated to reduced susceptibility to penicillins, was amplified and pyrosequenced. All results were in concordance with Sanger sequencing, and a high correlation between alterations in the two Peni-specific sites and reduced susceptibility to penicillins was identified. PMID:18070955

A real-time prospective evaluation of clinical pharmaco-economic impact of diagnostic label of 'penicillin allergy' in a UK teaching hospital.

PubMed

Li, M; Krishna, M T; Razaq, S; Pillay, D

2014-12-01

To perform a pharmaco-economic analysis of prescribing alternative antibiotics in patients with a diagnostic label of 'penicillin allergy' and assess whether collation of information from a structured history and liaison with the family physician could reduce costs. A prospective pro-forma-based interview of randomly selected in-patients and their family physician was used to assess the validity of the diagnostic label of 'penicillin allergy'. Cost analysis of prescription of alternative antibiotics was performed and compared with first-line agents. 102 patients were assessed and only 40% (n=41) were found to have a history consistent with penicillin hypersensitivity, 40% (n=41) were likely 'not allergic' and 20% (n=20) had 'indeterminate' reactions. Total cost of antibiotics prescribed for patients with penicillin allergy was 1.82-2.58-fold higher than for first-line antibiotics. Obtaining a structured history from the patient and family physician alone can enable an accurate identification of penicillin allergy status. Total acquisition cost of second-line antibiotics is higher than if these patients were prescribed first-line antibiotics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

PubMed

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.

Comparing performance of amoxicillin and intramuscular benzathine penicillin in relieving manifestations of streptococcal pharyngitis in children.

PubMed

Eslami, S T; Nassirian, A; Nassirian, H; Hatami, E; Sobhani, E; Najibpour, R

2014-12-01

To compare clinical and bacteriologic responses to intramuscular benzathine penicillin G (BPG) and single dose of amoxicillin in Group A streptococcal (GAS) pharyngitis. This study included 571 children from 6 to 15 years old age, with pharyngitis, who were admitted to 45 elementary and guidance schools from 7 regions of Education Organization in North-East of Iran, Mashhad. They were screened for enrollment and if he/she presented pharyngitis with clinical criteria of sore throat, erythema, exudate and tender or enlarged anterior cervical lymph nodes. Exclusion criteria included reports of antibiotic use, negative throat culture for GAS and history of allergy to the drugs. Clinical and bacteriologic responses to BPG and once daily orally amoxicillin were considered and compared. In the amoxicillin group, treatment failure was more than the penicillin group (18.9% vs. 6.4%, respectively) but the difference was not statistically significant (p < 0.05). Both drugs were significantly effective in reducing pharyngitis manifestations but penicillin was significantly more effective in reducing exudate than amoxicillin. Our study was in line with studies comparing the two drugs. The results show that once-daily therapy with amoxicillin is as effective as intramuscular benzathine penicillin G for the treatment of GAS pharyngitis, but penicillin was significantly more effective in reducing exudate and concurrent signs vs. amoxicillin.

Antimicrobial liquid formulations: a blind taste comparison of three brands of penicillin VK and three brands of amoxicillin.

PubMed

Chan, D S; Demers, D M; Bass, J W

1996-02-01

To rate the perception of taste, texture, smell and aftertaste of various brands of penicillin VK and amoxicillin. Oral, liquid formulations of three brands of penicillin VK (PenVee K, V-Cillin-K, VeeTids) and three brands of amoxicillin (Amoxil, Trimox, Wymox) were evaluated for smell, texture, taste, and aftertaste by 30 volunteers in a blind study. Each category was scored on a scale of 1 to 5. The order in which the drugs were sampled was randomized for the first three groups of five participants. The order then was reversed for the remaining three groups of participants. A 537-bed US Army teaching hospital. Participants included 30 healthy adult volunteers from the Departments of Pediatrics, Nursing, and Pharmacy. Drugs received cumulative scores in each category, as well as an overall total score ranking. The data were analyzed using one-way ANOVA for repeated measures with a post hoc Duncan's multiple range test to determine significant differences between individual means. Overall, Trimox and Amoxil scored significantly higher than the remaining drugs. Although V-Cillin-K scored highest in the smell category, its score was significantly below those of Trimox and Amoxil in the texture, taste, aftertaste, and overall categories. Overall, the three penicillin VK solutions scored lower than the three amoxicillin suspensions, with PenVee K ranking the lowest. Among the penicillin VK solutions, V-Cillin-K scored significantly higher overall than the other two penicillin VK solutions. Overall, all three amoxicillin oral, liquid suspensions that were studied scored significantly better than the three penicillin VK solutions.

An outbreak of penicillin resistant Streptococcus pneumoniae investigated by a polymerase chain reaction based genotyping method.

PubMed Central

Gillespie, S H; McHugh, T D; Hughes, J E; Dickens, A; Kyi, M S; Kelsey, M

1997-01-01

AIMS: To characterise the genotypes of penicillin resistant Streptococcus pneumoniae infecting patients in a care of the elderly ward and to study its transmission in a hospital environment. METHODS: Isolates of S pneumoniae were cultured from specimens obtained from patients who had been admitted to a care of the elderly ward where an outbreak had occurred. Penicillin resistant S pneumoniae were also obtained from a series of surveillance throat swabs taken from patients in the same ward. In addition, all penicillin resistant S pneumoniae isolated from specimens submitted for culture at the time of the outbreak were included. Four sensitive strains isolated from a routine microbiology laboratory were included as controls. A simple polymerase chain reaction (PCR) based genotyping method for the penicillin binding protein (PBP) genes 1a, 2x, and 2b was used to characterise the genotypes. RESULTS: Nine patients were infected with serotype 9 S pneumoniae. Four of these patients died; two deaths were directly attributable to the infection. Tested against a battery of haemolytic streptococci and other organisms found in the respiratory tract, only two false positive reactions for PBP 2x were found among S mitis. The method demonstrated that the outbreak strain had altered PBP 1a, 2b, and 2x genes, a pattern clearly distinguishable from other penicillin resistant strains isolated at the same time. CONCLUSIONS: This method is simple to perform and would enable many laboratories to characterise the genotype of penicillin resistant S pneumoniae and investigate transmission in their hospitals. Images PMID:9462268

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

PubMed

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.

Penicillin-resistant, ampicillin-susceptible Enterococcus faecalis of hospital origin: pbp4 gene polymorphism and genetic diversity.

PubMed

Conceição, Natália; da Silva, Lucas Emanuel Pinheiro; Darini, Ana Lúcia da Costa; Pitondo-Silva, André; de Oliveira, Adriana Gonçalves

2014-12-01

Despite the spread of penicillin-resistant, ampicillin-susceptible Enterococcus faecalis (PRASEF) isolates in diverse countries, the mechanisms leading to this unusual resistance phenotype have not yet been investigated. The aim of this study was to evaluate whether polymorphism in the pbp4 gene is associated with penicillin resistance in PRASEF isolates and to determine their genetic diversity. E. faecalis isolates were recovered from different clinical specimens of hospitalized patients from February 2006 to June 2010. The β-lactam minimal inhibitory concentrations (MICs) were determined by E-test®. The PCR-amplified pbp4 gene was sequenced with an automated sequencer. The genetic diversities of the isolates were established by PFGE (pulsed-field gel electrophoresis) and MLST (multilocus sequencing typing). Seventeen non-producing β-lactamase PRASEF and 10 penicillin-susceptible, ampicillin-susceptible E. faecalis (PSASEF) strains were analyzed. A single-amino-acid substitution (Asp-573→Glu) in the penicillin-binding domain was significantly found in all PRASEF isolates by sequencing of the pbp4 gene but not in the penicillin-susceptible isolates. In contrast to the PSASEF isolates, a majority of the PRASEFs had similar PFGE profiles. Six representative PRASEF isolates were resolved by MLST into ST9 and ST524 and belong to the globally dispersed clonal complex 9 (CC9). In conclusion, it appears quite likely that the amino acid alteration (Asp-573→Glu) found in the PBP4 of the Brazilian PRASEF isolates may account for their reduced susceptibility to penicillin, although other resistance mechanisms remain to be investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

Penicillin skin testing in patients with a history of beta-lactam allergy.

PubMed

del Real, Gonzalo Alvarez; Rose, Mark E; Ramirez-Atamoros, Maria T; Hammel, Jeffrey; Gordon, Steven M; Arroliga, Alejandro C; Arroliga, Mercedes E

2007-04-01

Vancomycin and fluoroquinolones are commonly used in patients with a history of penicillin allergy. To determine the safety and utility of penicillin skin testing (PST). Retrospective study of patients with a history of penicillin allergy between April 1, 1999, and September 30, 2004. Penicillin skin testing was performed by means of standard methods using benzylpenicilloyl-polysine, penicillin G, and histamine and saline controls. Of 596 patients studied, 25.3% were outpatients, 50.3% were inpatients, and 24.3% were intensive care unit patients. The most common antibiotics used during the time of PST were vancomycin and fluoroquinolones. Results of PST were negative in 88.4% of patients, positive in 8.2%, and indeterminate in 3.4%. One patient (0.17%) developed urticaria immediately after PST. Fifty-five percent of patients with negative PST results were changed to a beta-lactam drug, more frequently in the intensive care unit vs the outpatient setting (70.3% vs 8.6%; P < .001) and in adults vs patients younger than 18 years (58.6% vs 8.1%; P < .001). A beta-lactam antibiotic was used in 290 patients with negative PST results. Of the patients given beta-lactam antibiotics, 5 (1.7%) had adverse reactions: 2 had hives after 16 and 20 days of therapy, 1 had a nonspecific rash after 17 days of therapy, 1 had flushing and urticaria 3 hours after a test dose of piperacillin-tazobactam, and 1 had a pruritic rash after 12 hours of therapy. Patients with a history of penicillin allergy can safely use beta-lactam drugs if negative PST results.

Decrease of selective immunoglobulin E response to amoxicillin despite repeated administration of benzylpenicillin and penicillin V.

PubMed

Fernandez, T; Torres, M J; R-Pena, R; Fuentes, M S; Robles, S; Mayorga, C; Blanca, M

2005-12-01

Subjects with IgE responses to betalactams can develop selective or cross-reactive responses after the administration of penicillin derivatives. After the reaction, however, the hapten induces a boosting phenomenon, which may increase the titre and the affinity of the antibody, with the resulting risk of developing allergic reactions to other penicillins. To determine in subjects with selective responses to amoxicillin (AX) and good tolerance to benzylpenicillin (BP) and penicillin V (PV) whether the administration of these compounds induced any change in specificity, measured by either skin or in vitro testing, which could predict the appearance of cross-reactivity. Ten subjects with a selective response to AX were followed-up for 2 years with the periodic administration of penicillin G and V (Group A) and compared with another group composed of 10 persons with identical clinical characteristics but without repeated penicillin administration (Group B). Periodic in vitro and in vivo measurements of specific IgE antibodies were performed at 6-month intervals. Patients were randomized to Group A or B according to their order of inclusion. In both groups, skin test reactivity tended to decrease, and although greater in Group A, the difference was not significant compared with Group B. Median RAST values also decreased over time and showed no differences in the exposed group compared with the controls. One patient in Group A became positive to benzylpenicilloyl (BPO), despite becoming negative to AX. Subjects with selective IgE responses to side-chain-specific determinants seem to become negative, with no influence from subsequent administration of a closely related penicillin.

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

PubMed Central

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

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

PubMed Central

Bennedsgaard, Torben W; Thamsborg, Stig M; Aarestrup, Frank M; Enevoldsen, Carsten; Vaarst, Mette; Christoffersen, Anna B

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 and cross-sectional study. Methods 20 conventional herds, 18 organic herds that converted before 1995, and 19 herds converting to organic farming in 1999 or 2000 were included in the study. Herds converting to organic farming were sampled three times one year apart; the other herds were sampled once. Risk of infection was estimated based on somatic cell count, milk production, breed, age and lactation stage. Results The high-risk cows represented about 49 % of the cows in the herds. The overall prevalence of SA and SAr among these cows was 29% (95% confidence interval: 24%–34%) and 4% (95% confidence interval: 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 of bovine intramammary infection in Denmark. PMID:17125515

Unexpected individual clinical site variation in eradication rates of group a streptococci by penicillin in multisite clinical trials.

PubMed

Kaplan, Edward L; Oakes, J Michael; Johnson, Dwight R

2007-12-01

Previously, we reported an unexpectedly large percentage of failures by penicillin to eradicate group A streptococci (GAS) from the upper respiratory tract. Because penicillin has been the recommended therapy for the treatment of GAS pharyngitis, our report prompted controversy. Data from clinical trials in which our laboratory has participated demonstrated marked variation in GAS eradication rates among clinical sites. The reasons for such variation have never been adequately examined. We performed statistical analyses of site variation in eradication rates to assess the potential effect on reported reduced penicillin efficacy. Penicillin GAS eradication rates were compared using data from 4 large multisite pharyngitis treatment trials (75 clinical sites; 1158 subjects). Variation in eradication rates among clinical sites was statistically evaluated [chi(2) tests and generalized estimating equation (GEE) regression models]. There was significant site-to-site variation in GAS eradication rates in each of the trials (range, 17-100%; P < 0.005) as well as between separate trials (mean range, 58-69%; P < 0.033). GEE modeling indicated that GAS eradication rates were significantly higher for clinical sites participating in more than one clinical trial. The statistically significant site-to-site variation in penicillin eradication rates was related to factors (dependencies) at individual sites. Such factors may affect assessment of therapeutic efficacy and indicate a necessity for considering clinical site variation before reporting pooled efficacy data from multiple sites; combined data may result in misleading clinical implications. This is the first report documenting significant variation resulting from individual clinical site-related factors and offers a possible explanation for reduced penicillin eradication.

Safety of benzathine penicillin for preventing congenital syphilis: a systematic review.

PubMed

Galvao, Tais F; Silva, Marcus T; Serruya, Suzanne J; Newman, Lori M; Klausner, Jeffrey D; Pereira, Mauricio G; Fescina, Ricardo

2013-01-01

To estimate the risk of serious adverse reactions to benzathine penicillin in pregnant women for preventing congenital syphilis. We searched for clinical trials or cohorts that assessed the incidence of serious adverse reactions to benzathine penicillin in pregnant women and the general population (indirect evidence). MEDLINE, EMBASE, Scopus and other databases were searched up to December 2012. The GRADE approach was used to assess quality of evidence. Absolute risks of each study were calculated along with their 95% confidence intervals (95% CI). We employed the DerSimonian and Laird random effects model in the meta-analyses. From 2,765 retrieved studies we included 13, representing 3,466,780 patients. The studies that included pregnant women were conducted to demonstrate the effectiveness of benzathine penicillin: no serious adverse reactions were reported among the 1,244 pregnant women included. In the general population, among 2,028,982 patients treated, 4 died from an adverse reaction. The pooled risk of death was virtually zero. Fifty-four cases of anaphylaxis were reported (pooled absolute risk = 0.002%; 95% CI: 0%-0.003% I(2) = 12%). From that estimate, penicillin treatment would be expected to result in an incidence of 0 to 3 cases of anaphylaxis per 100,000 treated. Any adverse reactions were reported in 6,377 patients among 3,465,322 treated with penicillin (pooled absolute risk = 0.169%; 95% CI: 0.073%-0.265% I(2) = 97%). The quality of evidence was very low. Studies that assessed the risk of serious adverse events due to benzathine penicillin treatment in pregnant women were scarce, but no reports of adverse reactions were found. The incidence of severe adverse outcomes was very low in the general population. The risk of treating pregnant women with benzathine penicillin to prevent congenital syphilis appears very low and does not outweigh its benefits. Further research is needed to improve the quality of evidence.

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

PubMed

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.

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

PubMed Central

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

2016-01-01

Background 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. Objective To determine the frequency and predictors of optimal and adequate therapy in patients with MSSA bacteremia. Design Retrospective cohort. Participants Adult inpatients with MSSA bacteremia, January 2009 through October 2013. Main Measures 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. Key Results 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 <0.001). Adjusting for other factors, 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]). Conclusions 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. PMID:27438379

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

PubMed

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 < 0.01). In the RAST inhibition studies all drugs exhibited good inhibitory potencies, and in some instances the side-chain of the 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.

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

PubMed

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.

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

PubMed

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 <0.001). Adjusting for other factors, 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.

Improving the Effectiveness of Penicillin Allergy De-labeling.

PubMed

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 < .0001). Of 355 SPT/IDT patients, 3 (0.8%), all in the IMM group, had nonserious positive OC reactions to single dose 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.

21 CFR 520.390a - Chloramphenicol tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... Because of potential antagonism, chloramphenicol should not be administered simultaneously with penicillin.... Because of potential antagonism, chloramphenicol should not be administered simultaneously with penicillin...

21 CFR 520.390a - Chloramphenicol tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... Because of potential antagonism, chloramphenicol should not be administered simultaneously with penicillin.... Because of potential antagonism, chloramphenicol should not be administered simultaneously with penicillin...

Meningitis caused by Oerskovia xanthineolytica.

PubMed

Kailath, E J; Goldstein, E; Wagner, F H

1988-03-01

In summary, we describe a case of central nervous system infection with O. xanthineolytica in which the infecting microbe probably was engrafted on a ventricular shunt. The bacteria caused a smoldering meningitis that did not respond to penicillin and rifampin despite in vitro sensitivity, presumably because of inadequate cerebrospinal fluid penetration of the penicillin and the recognized difficulty of eradicating bacteria from contaminated shunts. Removal of the shunt and continued treatment with penicillin and rifampin resulted in cure.

Preferential Inhibition of Penicillinase Induction by Oxytetracycline and Its Effect on the Penicillin Susceptibility of Staphylococci

PubMed Central

Michael, Thomas M.; Michael, J. Gabriel; Massell, Benedict F.

1967-01-01

Exposure of penicillinase-producing staphylococci to a combination of penicillin and oxytetracycline resulted in a synergistic inhibitory activity of the antibiotics on the bacteria. Oxytetracycline was employed in concentrations having little or no effect on bacterial growth. It was found that the synergistic antibacterial effect was caused by the preferential inhibition of penicillinase induction by oxytetracycline, rendering the staphylococci more susceptible to penicillin. PMID:5182245

Herd-level association between antimicrobial use and antimicrobial resistance in bovine mastitis Staphylococcus aureus isolates on Canadian dairy farms.

PubMed

Saini, V; McClure, J T; Scholl, D T; DeVries, T J; Barkema, H W

2012-04-01

Surveillance of antimicrobial use and resistance is needed to manage antimicrobial resistance in bacteria. In this study, data were collected on antimicrobial use and resistance in Staphylococcus aureus (n=562), isolated from intramammary infections and (sub)clinical mastitis cases on 89 dairy farms in 4 regions of Canada [Alberta, Ontario, Québec, and the Maritime Provinces (Prince Edward Island, Nova Scotia, and New Brunswick)]. Dairy producers were asked to deposit empty drug containers into specially provided receptacles, and antimicrobial drug use rate was calculated to quantify antimicrobial use. Minimum inhibitory concentrations were determined using the Sensititer bovine mastitis plate system (TREK Diagnostic Systems Inc., Cleveland, OH), containing antimicrobials commonly used for mastitis treatment and control. Multivariable logistic regression models were built to determine herd-level risk factors of penicillin, ampicillin, pirlimycin, penicillin-novobiocin combination, tetracycline and sulfadimethoxine resistance in Staph. aureus isolates. Intramammary administration of the penicillin-novobiocin combination for dry cow therapy was associated with penicillin and ampicillin resistance [odds ratio (OR): 2.17 and 3.10, respectively]. Systemic administration of penicillin was associated with penicillin resistance (OR: 1.63). Intramammary administration of pirlimycin for lactating cow mastitis treatment was associated with pirlimycin resistance as well (OR: 2.07). Average herd parity was associated with ampicillin and tetracycline resistance (OR: 3.88 and 0.02, respectively). Average herd size was also associated with tetracycline resistance (OR: 1.02). Dairy herds in the Maritime region had higher odds of penicillin and lower odds of ampicillin resistance than dairy herds in Québec (OR: 2.18 and 0.19, respectively). Alberta dairy herds had lower odds of ampicillin and sulfadimethoxine resistance than dairy herds in Québec (OR: 0.04 and 0.08, respectively). Ontario dairy herds had lower odds of tetracycline and sulfadimethoxine resistance than dairy herds in Québec (OR: 0.05 and 0.33, respectively). Herd-level use of certain antimicrobials administered for mastitis treatment and control, such as intramammary penicillin and pirlimycin as well as systemically administered penicillin and florfenicol, was positively associated with antimicrobial resistance in bovine mastitis pathogens in the field conditions. Differences in antimicrobial resistance outcomes across 4 regions of Canada were observed. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

Reduction of fever and streptococcal bacteremia in granulocytopenic patients with cancer. A trial of oral penicillin V or placebo combined with pefloxacin. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

PubMed

1994-10-19

To determine the effect of oral penicillin V combined with a fluoroquinolone (pefloxacin) on the occurrence of fever and streptococcal and other gram-positive coccal bacteremic infections in granulocytopenic patients with cancer. Prospective randomized double-blinded placebo-controlled prophylactic trial. Inpatient setting in multiple cooperating cancer centers. Convenience sample with a total of 551 granulocytopenic patients, 95% of whom had leukemia or underwent bone marrow transplantation. Penicillin V (500 mg twice a day) vs placebo given in combination with oral pefloxacin (400 mg twice a day). Occurrence of fever and/or infection. Fever or infection (without fever) developed in 190 (71%) of 268 evaluable patients in the penicillin arm compared with 213 (80%) of 268 evaluable patients in the placebo arm (P = .03; 95% confidence interval [CI] for the difference, -16% to -1%). Bacteremia occurred in 58 (22%) of 268 placebo-treated patients and in 38 (14%) of 268 penicillin-treated patients (P = .03; 95% CI for the difference, -14% to -1%), primarily due to a reduction in streptococcal bacteremic episodes that occurred in 14 penicillin-treated patients (5%) and in 27 placebo-treated patients (10%) (P = .05; 95% CI for the difference, -9% to -0.3%). Gram-negative rod bacteremias occurred in only two patients (1%) and in five patients (2%), respectively. Logistic regression analysis also supported the treatment effect on the development of bacteremia. These results demonstrate that the addition of penicillin V to fluoroquinolone prophylaxis in granulocytopenic patients with cancer effectively reduces febrile episodes and the incidence of bacteremia, especially that due to streptococcal species.

Impact of the revised penicillin susceptibility breakpoints for Streptococcus pneumoniae on antimicrobial resistance rates of meningeal and non-meningeal pneumococcal strains.

PubMed

Al-Waili, Badria R; Al-Thawadi, Sahar; Hajjar, Sami Al

2013-01-01

In January 2008, the Clinical Laboratory Standard Institute (CLSI) revised the Streptococcus pneumoniae breakpoints for penicillin to define the susceptibility of meningeal and non-meningeal isolates. We studied the impact of these changes. In addition, the pneumococcal resistance rate to other antimicrobial agents was reviewed. Laboratory data on peumococcal isolates collected retrospectively from hospitalized children in tertiary care hospital in Riyadh, Saudi Arabia from January 2006 to March 2012. Only sterile samples were included from cerebrospinal fluids, blood, sterile body fluids and surgical tissue. Other samples such as sputum and non sterile samples were excluded. We included samples from children 14 years old or younger. The minimum inhibitory concentration (MIC) for penicillin, cefuroxime, ceftriaxone and meropenem were determined by using the E-test, while susceptibility to erythromycin, cotrimoxazole and vancomycin were measured using the disc diffusion methods following the guideline of CLSI. Specimens were analyzed in two different periods: from January 2006 to December 2007 and from January 2008 to March 2012. During the two periods there were 208 samples of which 203 were blood samples. Full penicillin resistance was detected in 6.6% in the first period. There was decrease in penicillin nonmeningeal resistance to 1.5% and an increase in resistance in penicillin meningeal 68.2% in the second period (P=.0001). There was an increase in rate of resistance among S pneumoniae isolates over the two periods to parenteral cefuroxime, erythromycin and cotrimoxazole by 34.6%, 35.5% and 51.9%, respectively. Total meropenem resistance found 4.3% and no vancomycin resistance was detected. The current study supports the use of the revised CLSI susceptibility breakpoints that promote using penicillin to treat nonmeningeal pneumococcal disease, and might slow the development of resistance to broader-spectrum antibiotics.

Antibacterial properties of (2,3)-alpha- and (2,3)-beta-methylene analogs of penicillin G.

PubMed Central

Christenson, J G; Pruess, D L; Talbot, M K; Keith, D D

1988-01-01

The penam nucleus can assume two conformations; these are designated open and closed. The synthetic (2,3)-alpha- and (2,3)-beta-methylenepenams can be regarded as analogs of the open and closed conformations, respectively. It has been shown that the beta-methylenepenams are essentially inactive, suggesting that the closed conformation of penams is also inactive. In this study, we investigated a series of beta-lactams, all of which contained phenylacetamido side chains: penicillin G, the (2,3)-alpha- and (2,3)-beta-methylenepenams, and the 3-acetoxymethyl- and 3-methylcephalosporins. The alpha-methylenepenam and penicillin G were the most active compounds, while the beta-methylene isomer was only poorly active. Results with permeability mutants suggested that the alpha-methylene compound penetrated the outer membrane somewhat more readily than penicillin G did. The intrinsic potency of the alpha-methylenepenam appeared to be similar to that of penicillin G, on the basis of their affinities for penicillin-binding proteins and their abilities to inhibit peptidoglycan synthesis in ether-permeabilized Escherichia coli, while the beta-methylene analog had very poor intrinsic potency. The alpha-methylene analog was about 10-fold more efficient (Vmax/Km) than penicillin G as a substrate for the cephalosporinases from Enterobacter cloacae and Proteus vulgaris, but it was about 40-fold less efficient with penicillinase from Staphylococcus aureus. These results strongly support the hypothesis that the active conformation of penams is the open conformation and suggest that the position in space of the carboxyl group relative to the beta-lactam carbonyl is an important determinant of cephalosporinlike character, as distinct from penicillinlike character. Images PMID:3190190

Trends in antibiotic resistance in Prevotella species from patients of the University Hospital of Maxillofacial Surgery, Sofia, Bulgaria, in 2003-2009.

PubMed

Boyanova, Lyudmila; Kolarov, Rossen; Gergova, Galina; Dimitrova, Liliana; Mitov, Ivan

2010-10-01

Head-and-neck infections often involve anaerobes such as Prevotella species. Aim of the present study was to assess the evolution and the factors associated with resistance in Prevotella species to penicillin, clindamycin, metronidazole, tetracycline and β-lactams/β-lactamase inhibitors (BL/BLIs). In total, 192 Prevotella strains, isolated from patients with oral and head-and-neck infections, were evaluated. Common isolates were Prevotella intermedia and Prevotella melaninogenica within the pigmented species as well as Prevotella oris and Prevotella oralis group within the non-pigmented species. Overall resistance was 43.2% for penicillin, 10.9% for clindamycin, 0% for metronidazole. Nonsusceptibility to tetracycline was 29.1% without significant differences in resistance rates between pigmented and other species. Penicillin resistant strains were β-lactamase positive. From 2003-2004 to 2007-2009, penicillin resistance rates increased about four-fold (from 15.4% to 60.6%). Clindamycin resistance did not show evolution, whereas tetracycline nonsusceptibility decreased from 43.3% in 2003-2004 to 20.7% in 2007-2009. Except for one (0.5%) P. oralis strain with intermediate susceptibility to BL/BLIs, the other strains were susceptible to the agents. In conclusion, in Prevotella strains from patients with head-and-neck infections, the resistance rate to penicillin increased, that to clindamycin remained stable and the nonsusceptibility rate to tetracycline decreased during the period. Activity against >99% of Prevotella strains was observed with metronidazole and BL/BLIs. The penicillin resistance and tetracycline nonsusceptibility were associated with the year of study, national antibiotic consumption and possibly with previous treatment (for tetracycline). The evolution of penicillin resistance in Prevotella strains was highly dynamic. Copyright © 2010 Elsevier Ltd. All rights reserved.

Nasal Carriage in Vietnamese Children of Streptococcus pneumoniae Resistant to Multiple Antimicrobial Agents

PubMed Central

Parry, Christopher M.; Diep, To Song; Wain, John; Hoa, Nguyen Thi Tuyet; Gainsborough, Mary; Nga, Diem; Davies, Catrin; Phu, Nguyen Hoan; Hien, Tran Tinh; White, Nicholas J.; Farrar, Jeremy J.

2000-01-01

Resistance to antimicrobial agents in Streptococcus pneumoniae is increasing rapidly in many Asian countries. There is little recent information concerning resistance levels in Vietnam. A prospective study of pneumococcal carriage in 911 urban and rural Vietnamese children, of whom 44% were nasal carriers, was performed. Carriage was more common in children <5 years old than in those ≥5 years old (192 of 389 [49.4%] versus 212 of 522 [40.6%]; P, 0.01). A total of 136 of 399 isolates (34%) had intermediate susceptibility to penicillin (MIC, 0.1 to 1 mg/liter), and 76 of 399 isolates (19%) showed resistance (MIC, >1.0 mg/liter). A total of 54 of 399 isolates (13%) had intermediate susceptibility to ceftriaxone, and 3 of 399 isolates (1%) were resistant. Penicillin resistance was 21.7 (95% confidence interval, 7.0 to 67.6) times more common in urban than in rural children (35 versus 2%; P, <0.001). More than 40% of isolates from urban children were also resistant to erythromycin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline. Penicillin resistance was independently associated with an urban location when the age of the child was controlled for. Multidrug resistance (resistance to three or more antimicrobial agent groups) was present in 32% of isolates overall but in 39% of isolates with intermediate susceptibility to penicillin and 86% of isolates with penicillin resistance. The predominant serotypes of the S. pneumoniae isolates were 19, 23, 14, 6, and 18. Almost half of the penicillin-resistant isolates serotyped were serotype 23, and these isolates were often multidrug resistant. This study suggests that resistance to penicillin and other antimicrobial agents is common in carriage isolates of S. pneumoniae from children in Vietnam. PMID:10681307

Cross-reactivity and tolerability of aztreonam and cephalosporins in subjects with a T cell-mediated hypersensitivity to penicillins.

PubMed

Romano, Antonino; Gaeta, Francesco; Valluzzi, Rocco Luigi; Maggioletti, Michela; Caruso, Cristiano; Quaratino, Donato

2016-07-01

The few studies performed in adults with T cell-mediated hypersensitivity to penicillins have found a rate of cross-reactivity with cephalosporins ranging from 2.8% to 31.2% and an absence of cross-reactivity with aztreonam. We sought to evaluate the possibility of using cephalosporins and aztreonam in subjects with documented delayed hypersensitivity to penicillins who especially require them. We conducted a prospective study of 214 consecutive subjects who had 307 nonimmediate reactions to penicillins (almost exclusively aminopenicillins) and had positive patch test and/or delayed-reading skin test responses to at least 1 penicillin reagent. To assess cross-reactivity with cephalosporins and aztreonam and the tolerability of such alternative β-lactams, all subjects underwent skin tests with cephalexin, cefaclor, cefadroxil, cefuroxime, ceftriaxone, and aztreonam. Subjects with negative responses were challenged with the alternative β-lactams concerned. All subjects had negative skin test results to cefuroxime, ceftriaxone, and aztreonam and tolerated challenges. Forty (18.7%) of the 214 subjects had positive skin test responses to at least 1 aminocephalosporin. Of the 174 subjects with negative responses, 170 underwent challenges; 1 reacted to cefaclor. These data demonstrate a rate of cross-reactivity between aminopenicillins and aminocephalosporins (ie, cephalexin, cefaclor, and cefadroxil) of around 20%, as well as the absence of cross-reactivity between penicillins and cefuroxime, ceftriaxone, and aztreonam in all subjects with T cell-mediated hypersensitivity to penicillins, almost exclusively aminopenicillins. Therefore these subjects could be treated with cefuroxime, ceftriaxone, and aztreonam. In those who especially require cephalosporin or aztreonam treatment, however, we recommend pretreatment skin tests because negative responses indicate tolerability. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Crystal Structures of Penicillin-Binding Protein 2 From Penicillin-Susceptible And -Resistant Strains of Neisseria Gonorrhoeae Reveal An Unexpectedly Subtle Mechanism for Antibiotic Resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powell, A.J.; Tomberg, J.; Deacon, A.M.

Penicillin-binding protein 2 (PBP2) from N. gonorrhoeae is the major molecular target for {beta}-lactam antibiotics used to treat gonococcal infections. PBP2 from penicillin-resistant strains of N. gonorrhoeae harbors an aspartate insertion after position 345 (Asp-345a) and 4-8 additional mutations, but how these alter the architecture of the protein is unknown. We have determined the crystal structure of PBP2 derived from the penicillin-susceptible strain FA19, which shows that the likely effect of Asp-345a is to alter a hydrogen-bonding network involving Asp-346 and the SXN triad at the active site. We have also solved the crystal structure of PBP2 derived from themore » penicillin-resistant strain FA6140 that contains four mutations near the C terminus of the protein. Although these mutations lower the second order rate of acylation for penicillin by 5-fold relative to wild type, comparison of the two structures shows only minor structural differences, with the positions of the conserved residues in the active site essentially the same in both. Kinetic analyses indicate that two mutations, P551S and F504L, are mainly responsible for the decrease in acylation rate. Melting curves show that the four mutations lower the thermal stability of the enzyme. Overall, these data suggest that the molecular mechanism underlying antibiotic resistance contributed by the four mutations is subtle and involves a small but measurable disordering of residues in the active site region that either restricts the binding of antibiotic or impedes conformational changes that are required for acylation by {beta}-lactam antibiotics.« less

Antimicrobial Susceptibility of Udder Pathogens Isolated from Dairy Herds in the West Littoral Region of Uruguay

PubMed Central

2002-01-01

A total of 522 strains belonging to streptococci, enterococci and staphylococci isolated from sub-clinical and clinical cases of bovine mastitis from the west littoral region of Uruguay were analysed for their susceptibility to several antimicrobial agents. The susceptibility patterns were studied by agar disk diffusion methods (ADDM) and broth micro-dilution to determine the minimum inhibitory concentration (MIC). The concentration that inhibits 90% (MIC90) of the analysed strains reported in micrograms per millilitre, for Staphylococcus aureus were > 8, 8, ≤ 0.5, ≤ 4, ≤ 1, ≤ 0.5, > 64, ≤ 0.25, 0.5, ≤ 1 and ≤ 1 to penicillin, ampicillin, oxacillin, cephalotin, gentamicin, erythromycin, oxitetracycline, enrofloxacin, trimethoprim/sulfamethoxazole, neomycin, and clindamycin, respectively. Coagulase-negative staphylococci (CNS) had different values for penicillin (4) and ampicillin (2), while the other antimicrobial agents had the same MIC90 values as reported for S. aureus. The MIC90 values for streptococci were 0.12, 0.25, ≤ 4, 16, ≤ 0.25, 0.5, 0.25 for penicillin, ampicillin, cephalotin, gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, whereas MIC90 for enterococci were 4, 4, 4, ≤ 0.5, 2, > 8 for penicillin, ampicillin, gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, respectively. Of 336 strains of S. aureus, 160 (47.6%) were resistant to penicillin. For 41 CNS strains, 10 (27%) presented penicillin-resistance. All the streptococcal strains were susceptible to penicillin, while 3 (7%) of the 43 enteroccocal strains were resistant. Non significant statistical differences were found between the results obtained by ADDM and broth micro-dilution for classifying bacterial isolates as susceptible or resistant according to the National Committee of Clinical Laboratory Standards. PMID:12071114

Modelling Neurofibroma Formation in the Culture Dish.

DTIC Science & Technology

1996-10-01

Eagle’s medium (DMEM) with high glucose (GIBCO cat # 11965-050) supplemented with 10 vol.% heat inactivated fetal bovine serum and penicillin /streptomycin...to approximately 10 ml of Dulbecco’s Modified Eagle Medium (DMEM, Gibco) supplemented with 10% fetal bovine serum (FBS, Gibco) and 1% penicillin ...dish containing 10-15 mls of DMEM, 10% FBS, 1% penicillin -streptomycin and maintained at 35oC and 7.5% C02 for several days until the cells were nearly

21 CFR 558.4 - Requirement of a medicated feed mill license.

Code of Federal Regulations, 2013 CFR

2013-04-01

.../ton 75-125. Oxytetracycline 90-120 20.0 g/lb (4.4%) 75-125/65-135. Penicillin 80-120 10.0 g/lb (2.2... 85-115 10.0 g/lb (2.2%) 85-125/70-130. Penicillin 85-115 5.0 g/lb (1.1%) 85-125/70-130.../lb (2.2%) 70-130. Penicillin 80-120 5.0 g/lb (1.1%) 70-130. Thiabendazole 94-106 45.4 g/lb (10.0%) >7...

21 CFR 558.4 - Requirement of a medicated feed mill license.

Code of Federal Regulations, 2011 CFR

2011-04-01

.../ton 75-125. Oxytetracycline 90-120 20.0 g/lb (4.4%) 75-125/65-135. Penicillin 80-120 10.0 g/lb (2.2... 10.0 g/lb (2.2%) 85-125/70-130. Penicillin 85-115 5.0 g/lb (1.1%) 85-125/70-130. Sulfamethazine 85.../lb (2.2%) 70-130. Penicillin 80-120 5.0 g/lb (1.1%) 70-130. Thiabendazole 94-106 45.4 g/lb (10.0%) >7...

21 CFR 558.4 - Requirement of a medicated feed mill license.

Code of Federal Regulations, 2012 CFR

2012-04-01

.../ton 75-125. Oxytetracycline 90-120 20.0 g/lb (4.4%) 75-125/65-135. Penicillin 80-120 10.0 g/lb (2.2... 10.0 g/lb (2.2%) 85-125/70-130. Penicillin 85-115 5.0 g/lb (1.1%) 85-125/70-130. Sulfamethazine 85.../lb (2.2%) 70-130. Penicillin 80-120 5.0 g/lb (1.1%) 70-130. Thiabendazole 94-106 45.4 g/lb (10.0%) >7...

Penicillin reduces eustachian tube gland tissue changes in acute otitis media.

PubMed

Andersen, Henrik; Thomsen, Jens; Cayé-Thomasen, Per

2005-08-01

The volume of the mucous paratubal glands and the number of the mucus-producing goblet cells in the middle ear and Eustachian tube (ET) are increased after experimental acute otitis media (AOM). The present investigation examines a potential effect of penicillin on the changes in goblet cell density and gland structures of the ET during and after AOM. Middle ear inoculation of Streptococcus pneumoniae in 50 rats. Two days later, 25 rats were given penicillin V as one daily dose for 5 days. Twenty-five rats received no treatment. Five animals from each group were sacrificed on days 4, 8, 16, 90, and 180. The ET was dissected and decalcified, followed by paraffin embedding, serial transverse sectioning, and PAS/alcian blue staining. The goblet cell density and the paratubal gland composition and volume were determined in every 20th section, using a light microscope. Penicillin reduced the increase of goblet cell density from day 8 and through 6 months, whereas the increase of the paratubal mucous gland volume was unaffected by treatment. We conclude that penicillin reduces the increase of ET goblet cell density during and after acute otitis media, whereas the paratubal gland volume remains unaffected. An increased mucosal secretory capacity and indicated excessive secretion of mucus may contribute to the deteriorated ET function found after AOM and thus predispose, sustain, or aggravate middle ear disease. This may be prevented by penicillin treatment.

[Improvement of the knowledge on allergic cross-reactions between two drug groups: beta-lactams and NSAIDS].

PubMed

Sánchez-Quiles, I; Nájera-Pérez, M D; Calleja-Hernández, M Á; Martinez-Martínez, F; Belchí-Hernández, J; Canteras, M

2013-01-01

To identify opportunities for improving the available knowledge of health care professionals (particularly, physicians, pharmacists, and nurses) on crossed allergic reactions (CAR) to penicillins and NSAIDs. Quasi-experimental prospective pre-exposure study at a 412-beds hospital. An assessment of the knowledge on CAR to penicillins and NSAIDs was performed by means of anonymous questionnaires before (1st questionnaire) and after (2d questionnaire) the implementation of a series of improvement measures: protocol of "patient allergic to drugs", pocket card, poster with summarized information, and informative talks. The questionnaires served as the CRF and the statistical analysis was done with the SPSS v18.0 software. The mean number of errors in the first questionnaire on CARs of penicillin allergic patient and on CARs of NSAIDs allergic patients was 20.53 and 27.62, respectively. The mean number of errors in the second questionnaire on CARs of penicillin allergic patient and on CARs of NSAIDs allergic patients was 2.27 and 7.26, respectively. All the results were significant for a p level < 0.005. - There is insufficient knowledge on CARs to penicillins and NSAIDS, which justifies improvement measures. - After the implementation of improvement measures, there is an increased knowledge on CARs to penicillins and NSAIDs in the study groups. Copyright © 2013 SEFH. Published by AULA MEDICA. All rights reserved.

Electronic structure and physicochemical properties of selected penicillins

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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.

Ampicillin

MedlinePlus

... Ampicillin is in a class of medications called penicillins. It works by killing bacteria.Antibiotics such as ... and pharmacist if you are allergic to ampicillin; penicillins; cephalosporin antibiotics such as cefaclor, cefadroxil, cefazolin (Ancef, ...

Amoxicillin

MedlinePlus

... Amoxicillin is in a class of medications called penicillin-like antibiotics. It works by stopping the growth ... and pharmacist if you are allergic to amoxicillin; penicillin antibiotics; cephalosporin antibiotics such as cefaclor, cefadroxil, cefazolin ( ...

Syphilis

MedlinePlus

... baby. Treatment Most often, syphilis is treated with penicillin given by a shot. This treatment has been ... Is The Prognosis? The treatment of syphilis with penicillin can resolve the infection. Patients should have blood ...

Minocycline

MedlinePlus

... used in patients who cannot be treated with penicillin to treat certain types of food poisoning, and ... Ergomar, in Cafergot, Migergot), and methylergonovine (Methergine); and penicillin. Also tell your doctor or pharmacist if you ...

Dicloxacillin

MedlinePlus

... Dicloxacillin is in a class of medications called penicillins. It works by killing bacteria.Antibiotics such as ... pharmacist if you are allergic to dicloxacillin, other penicillin antibiotics, cephalosporin antibiotics such as cefaclor, cefadroxil, cefazolin ( ...

Sickle Cell Disease (For Teens)

MedlinePlus

... help relieve the pain of sickle cell crises. Penicillin or other antibiotics can help prevent infections, though doctors usually stop giving penicillin to kids who have sickle cell disease after ...

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

PubMed

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.

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

PubMed

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.

Molding national research systems: the introduction of penicillin to Germany and France.

PubMed

Gaudillière, Jean-Paul; Gausemeier, Bernd

2005-01-01

In our historical imagination, penicillin plays the role of the good sister of the atomic bomb. It epitomizes the success of the U.S. scientific mobilization and the emergence of modem biomedicine. This chapter discusses the fate of penicillin in France and Germany, comparing the reactions of the two countries to the antibiotic challenge under restricted conditions. The comparison centers on the scientific and industrial practices that created penicillin. It also sheds light on the professional styles, forms of expertise, and political resources that helped shape the meanings and uses of the antibiotic. The French section recounts how the Pasteur Institute and the military administration organized penicillin research and production during 1945-1947. The alliance between the two has roots in the highly peculiar political and social climate of the liberation and in the biotechnological tradition of the Pasteur Institute. The German section focuses on the Kaiser Wilhelm Institute for Biochemistry. The study of the institute, which worked closely with a pharmaceutical company, features the interplay between academic chemists and industry, while providing insights into the research organization under National Socialism.

Oxacillin Injection

MedlinePlus

... injection is in a class of medications called penicillins. It works by killing bacteria.Antibiotics such as ... and pharmacist if you are allergic to oxacillin; penicillins; cephalosporin antibiotics such as cefaclor, cefadroxil, cefazolin, cefdinir, ...

Gas Gangrene

MedlinePlus

... Surgically removing the dead and infected tissue Administering penicillin intravenously Managing shock and other complications Possibly treating ... it with water and start antibiotics such as penicillin or clindamycin. Last Updated 11/21/2015 Source ...

Nafcillin Injection

MedlinePlus

... injection is in a class of medications called penicillins. It works by killing bacteria.Antibiotics such as ... and pharmacist if you are allergic to nafcillin; penicillins; cephalosporin antibiotics such as cefaclor, cefadroxil, cefazolin, cefdinir, ...

Anaerobic Infections

MedlinePlus

... doctor may treat it with intravenous antibiotics (eg, penicillin, ampicillin) for 4 to 6 weeks, followed by ... In most cases, the bacteria are resistant to penicillin drugs. If an abscess has formed, it may ...

Ampicillin Injection

MedlinePlus

... injection is in a class of medications called penicillins. It works by killing bacteria.Antibiotics such as ... and pharmacist if you are allergic to ampicillin; penicillins; cephalosporin antibiotics such as cefaclor, cefadroxil, cefazolin (Ancef, ...

Activity of Amoxicillin-Clavulanate against Penicillin-Resistant Streptococcus pneumoniae in an Experimental Respiratory Infection Model in Rats†

PubMed Central

Smith, Gillian M.; Slocombe, Brian; Abbott, Karen H.; Mizen, Linda W.

1998-01-01

High doses of amoxicillin, equivalent to those produced by 500- and 750-mg oral doses in humans (area under the plasma concentration-time curve), were effective against a penicillin-resistant strain of Streptococcus pneumoniae in an experimental respiratory tract infection in immunocompromised rats; this superior activity confirms the results of previous studies. An unexpected enhancement of amoxicillin’s antibacterial activity in vivo against penicillin-resistant and -susceptible S. pneumoniae strains was observed when subtherapeutic doses of amoxicillin were coadministered with the β-lactamase inhibitor potassium clavulanate. The reason for this enhancement was unclear since these organisms do not produce β-lactamase. The differential binding of clavulanic acid and amoxicillin to penicillin-binding proteins may have contributed to the observed effects. PMID:9559788

Efficacy of high doses of oral penicillin versus amoxicillin in the treatment of adults with non-severe pneumonia attended in the community: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Streptococcus pneumoniae is the bacterial agent which most frequently causes pneumonia. In some Scandinavian countries, this infection is treated with penicillin V since the resistances of pneumococci to this antibiotic are low. Four reasons justify the undertaking of this study; firstly, the cut-off points which determine whether a pneumococcus is susceptible or resistant to penicillin have changed in 2008 and according to some studies published recently the pneumococcal resistances to penicillin in Spain have fallen drastically, with only 0.9% of the strains being resistant to oral penicillin (minimum inhibitory concentration>2 μg/ml); secondly, there is no correlation between pneumococcal infection by a strain resistant to penicillin and therapeutic failure in pneumonia; thirdly, the use of narrow-spectrum antibiotics is urgently needed because of the dearth of new antimicrobials and the link observed between consumption of broad-spectrum antibiotics and emergence and spread of antibacterial resistance; and fourthly, no clinical study comparing amoxicillin and penicillin V in pneumonia in adults has been published. Our aim is to determine whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of uncomplicated community-acquired pneumonia. Methods We will perform a parallel group, randomised, double-blind, trial in primary healthcare centres in Spain. Patients aged 18 to 65 without significant associated comorbidity attending the physician with signs and symptoms of lower respiratory tract infection and radiological confirmation of the diagnosis of pneumonia will be randomly assigned to either penicillin V 1.6 million units thrice-daily during 10 days or amoxicillin 1,000 mg thrice-daily during 10 days. The main outcome will be clinical cure at 14 days, defined as absence of fever, resolution or improvement of cough, improvement of general wellbeing and resolution or reduction of crackles indicating that no other antimicrobial treatment will be necessary. Any clinical result other than the anterior will be considered as treatment failure. A total of 210 patients will be recruited to detect a non-inferiority margin of 15% between the two treatments with a minimum power of 80% considering an alpha error of 2.5% for a unilateral hypothesis and maximum possible losses of 15%. Discussion This pragmatic trial addresses the long-standing hypothesis that the administration of high doses of a narrow-spectrum antibiotic (penicillin V) in patients with non-severe pneumonia attended in the community is not less effective than high doses of amoxicillin (treatment currently recommended) in patients under the age of 65 years. Trial registration EudraCT number 2012-003511-63. PMID:23594463

21 CFR 520.90a - Ampicillin capsules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... animals with a history of an allergic reaction to any of the penicillins. Ampicillin is contraindicated in... penicillins. Ampicillin is contraindicated in infections caused by penicillinase-producing organisms. Not for...

21 CFR 520.90a - Ampicillin capsules.

Code of Federal Regulations, 2013 CFR

2013-04-01

... animals with a history of an allergic reaction to any of the penicillins. Ampicillin is contraindicated in... penicillins. Ampicillin is contraindicated in infections caused by penicillinase-producing organisms. Not for...

21 CFR 520.90a - Ampicillin capsules.

Code of Federal Regulations, 2014 CFR

2014-04-01

... animals with a history of an allergic reaction to any of the penicillins. Ampicillin is contraindicated in... penicillins. Ampicillin is contraindicated in infections caused by penicillinase-producing organisms. Not for...

Allergy Skin Tests

MedlinePlus

... allergic rhinitis) Allergic asthma Dermatitis (eczema) Food allergies Penicillin allergy Bee venom allergy Latex allergy Skin tests ... check for an allergy to insect venom or penicillin. Patch test Patch testing is generally done to ...

21 CFR 520.90a - Ampicillin capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... animals with a history of an allergic reaction to any of the penicillins. Ampicillin is contraindicated in... penicillins. Ampicillin is contraindicated in infections caused by penicillinase-producing organisms. Not for...

Tabes Dorsalis

MedlinePlus

... co-associated HIV infection. View Full Definition Treatment Penicillin, administered intravenously, is the treatment of choice. Associated ... an individual with tabes dorsalis is important. × Treatment Penicillin, administered intravenously, is the treatment of choice. Associated ...

21 CFR 520.90a - Ampicillin capsules.

Code of Federal Regulations, 2012 CFR

2012-04-01

... animals with a history of an allergic reaction to any of the penicillins. Ampicillin is contraindicated in... penicillins. Ampicillin is contraindicated in infections caused by penicillinase-producing organisms. Not for...

Research in Drug Development against Viral Diseases of Military Importance (Biological Testing). Volume 1

DTIC Science & Technology

1991-03-01

Nu serum, 10 mM HEPES buffer, 2 mM glutamine, 1 mM sodium pyruvate, and penicillin /streptomycin (at 100 units and 100 pg/ml, respectively) and...inactivated fetal bovine serum, 100 units penicillin per ml, and 100 pg streptomycin per ml (EMEM + 10% or 5% heat-inactivated fbs). From November 16...4 mM glutamine, 15% heat-inactivated fetal bovine serum, antibiotics (SO units of penicillin and SO pg of streptomycin per ml), and SO units of

ANTIBIOTICS IN MANAGEMENT OF STAPHYLOCOCCAL ENDOCARDITIS—With Special Reference to Increasing Bacterial Resistance

PubMed Central

Levinson, David C.; Griffith, George C.; Pearson, Harold E.

1951-01-01

Eighteen patients with staphylococcal endocarditis were observed at the Los Angeles County Hospital over a 3-year period (1947-49, inclusive). Twelve died. Bacterial sensitivity studies were carried out in 15 of the cases, and there was resistance to penicillin in ten. Aureomycin was effective in two cases of Staphylococcus aureus endocarditis in which there was no response to penicillin therapy. In one case of Staphylococcus aureus endocarditis the organism was resistant to penicillin and developed increasing resistance to aureomycin. PMID:14812349

Beta-lactam antibiotics: newer formulations and newer agents.

PubMed

Martin, Stanley I; Kaye, Kenneth M

2004-09-01

beta-Lactam antibiotics share a common structure and mechanism of action, although they differ in their spectrum of antimicrobial activity and utility in treating different infections. The current classes include the penicillins, the penicillinase-resistant penicillins, the extended- spectrum penicillins, the cephalosporins, the carbapenems, and the monobactams. This article discusses some of the newest beta-lactams available for use in the United States: ertapenem, cefditoren, and cefepime. A new formulation of amoxicillin-clavulanate, which contains higher doses of amoxicillin, is also discussed.

21 CFR 558.4 - Requirement of a medicated feed mill license.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 90-120 20.0 g/lb (4.4%) 75-125/65-135. Penicillin 80-120 10.0 g/lb (2.2%) 65-135. Poloxalene 90-110... 10.0 g/lb (2.2%) 85-125/70-130. Penicillin 85-115 5.0 g/lb (1.1%) 85-125/70-130. Sulfamethazine 85.... Chlortetracycline 85-125 10.0g/lb (2.2%) 70-130. Penicillin 80-120 5.0 g/lb (1.1%) 70-130. Thiabendazole 94-106 45.4...

Amoxicillin and Clavulanic Acid

MedlinePlus

... Amoxicillin is in a class of medications called penicillin-like antibiotics. It works by stopping the growth ... allergic to amoxicillin (Amoxil, Trimox, Wymox), clavulanic acid, penicillin, cephalosporins, or any other medications.tell your doctor ...

Neurological Complications of AIDS

MedlinePlus

... antimalarial drugs to combat certain bacterial infections, and penicillin to treat neurosyphilis. Aggressive antiretroviral therapy is used ... antimalarial drugs to combat certain bacterial infections, and penicillin to treat neurosyphilis. Aggressive antiretroviral therapy is used ...

STDs and Pregnancy

MedlinePlus

... Status of EPT Legal/Policy Toolkit Gemifloxacin Procaine Penicillin G Shortage Additional Resources Archive Drug Notices Azithromycin ... Pyloric Stenosis Cefixime Spectinomycin – Alternative Treatments Alternatives to Penicillin G Updating the STD Treatment Guidelines 2010 Guidelines ...

Ampicillin and Sulbactam Injection

MedlinePlus

... Ampicillin is in a class of medications called penicillin-like antibiotics. It works by stopping the growth ... pharmacist if you are allergic to ampicillin; sulbactam; penicillin antibiotics; cephalosporin antibiotics such as cefaclor, cefadroxil, cefazolin ( ...

STDs and Infertility

MedlinePlus

... Status of EPT Legal/Policy Toolkit Gemifloxacin Procaine Penicillin G Shortage Additional Resources Archive Drug Notices Azithromycin ... Pyloric Stenosis Cefixime Spectinomycin – Alternative Treatments Alternatives to Penicillin G Updating the STD Treatment Guidelines 2010 Guidelines ...

Piperacillin and Tazobactam Injection

MedlinePlus

... Piperacillin is in a class of medications called penicillin antibiotics. It works by killing bacteria that cause ... and cephalexin (Keflex); beta-lactam antibiotics such as penicillin or amoxicillin (Amoxil, Larotid, Moxatag); any other medications, ...

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

PubMed Central

Olatoye, Isaac Olufemi; Daniel, Oluwayemisi Folashade; Ishola, Sunday Ayobami

2016-01-01

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’ extension education on alternatives to antibiotic prophylaxis, veterinary prescriptions and withdrawal periods are recommended to prevent residues. PMID:27733794

Penicillin to prevent recurrent leg cellulitis.

PubMed

Thomas, Kim S; Crook, Angela M; Nunn, Andrew J; Foster, Katharine A; Mason, James M; Chalmers, Joanne R; Nasr, Ibrahim S; Brindle, Richard J; English, John; Meredith, Sarah K; Reynolds, Nicholas J; de Berker, David; Mortimer, Peter S; Williams, Hywel C

2013-05-02

Cellulitis of the leg is a common bacterial infection of the skin and underlying tissue. We compared prophylactic low-dose penicillin with placebo for the prevention of recurrent cellulitis. We conducted a double-blind, randomized, controlled trial involving patients with two or more episodes of cellulitis of the leg who were recruited in 28 hospitals in the United Kingdom and Ireland. Randomization was performed according to a computer-generated code, and study medications (penicillin [250 mg twice a day] or placebo for 12 months) were dispensed by a central pharmacy. The primary outcome was the time to a first recurrence. Participants were followed for up to 3 years. Because the risk of recurrence was not constant over the 3-year period, the primary hypothesis was tested during prophylaxis only. A total of 274 patients were recruited. Baseline characteristics were similar in the two groups. The median time to a first recurrence of cellulitis was 626 days in the penicillin group and 532 days in the placebo group. During the prophylaxis phase, 30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to prevent one recurrent cellulitis episode of 5 (95% CI, 4 to 9). During the no-intervention follow-up period, there was no difference between groups in the rate of a first recurrence (27% in both groups). Overall, participants in the penicillin group had fewer repeat episodes than those in the placebo group (119 vs. 164, P=0.02 for trend). There was no significant between-group difference in the number of participants with adverse events (37 in the penicillin group and 48 in the placebo group, P=0.50). In patients with recurrent cellulitis of the leg, penicillin was effective in preventing subsequent attacks during prophylaxis, but the protective effect diminished progressively once drug therapy was stopped. (Funded by Action Medical Research; PATCH I Controlled-Trials.com number, ISRCTN34716921.).

Seasonal Flu and Staph Infection

MedlinePlus

... infections are treated with an antibiotic related to penicillin. However, over the past 50 years, some staph ... become resistant to antibiotics, including the commonly used penicillin-related antibiotics. These resistant bacteria are called methicillin- ...

Group B Strep Infection: Prevention in Newborns

MedlinePlus

... quickly; doctors cannot give antibiotics before labor begins. Penicillin is the most common antibiotic that doctors prescribe, ... antibiotics to women who are severely allergic to penicillin. Women should tell their doctor or nurse about ...

Group B Streptococcus and Pregnancy

MedlinePlus

... are positive? • What if I am allergic to penicillin? • What if I already had a baby who ... bacteria may regrow and be present during labor. Penicillin is the antibiotic that is most often given ...

Regulation and the circulation of knowledge: penicillin patents in Spain.

PubMed

Romero de Pablos, Ana

2011-01-01

This paper tells the early history of penicillin patenting in Spain. Patents turn out to be useful instruments for analysing the management of knowledge and its circulation in different professional and geographical domains. They protected knowledge while contributing to standardisation. Patents also ensured quality and guaranteed reliability in manufacturing, delivering and prescribing new drugs. They gained special prominence by allowing the creation of a network in which political, economic and business, industrial power, public health and international cooperation fields came together. The main source of information used for this purpose has been the earliest patent applications for penicillin in Spain between 1948 and 1950, which are kept in the Historical Archives of the Oficina Española de Patentes y Marcas. The study of these patents for penicillin shows their role as agents in introducing this drug in Spain.

The continuing threat of syphilis in pregnancy.

PubMed

Moline, Heather R; Smith, James F

2016-04-01

Syphilis in pregnancy continues to be a worldwide threat to mothers and their fetuses, and in recent years has been increasing in prevalence. The purpose of this short review is to address current issues in the diagnosis and management of syphilis complicating pregnancies. Maternal syphilis infections and congenital syphilis appear to be increasing in both high and low resource settings. Treponema pallidum ssp. pallidum, the causative spirochete of syphilis, remains one of the few human infectious pathogens that has not been successfully cultured, making identification difficult and research in targeted antimicrobial therapies challenging. Fortunately, syphilis remains sensitive to penicillin, which remains the foundational therapy for this infection. Patients with syphilis and significant penicillin allergies remain a specific challenge in treatment. Of concern is the emergence of T. pallidum resistant to macrolides such as azithromycin. This will limit options in patients with penicillin allergies, and potentially contribute to suboptimal treatment. During pregnancy, penicillin is the only known effective treatment for congenital syphilis, and pregnant patients with penicillin allergy should be desensitized and treated with penicillin. Research focusing on protein expression of the genome of T. pallidum may lead to more accurate screening and diagnosis and development of novel antibiotic therapies. Obstetric and pediatric providers, public health organizations, and governments should recognize the re-emergence of syphilis globally and in their local healthcare environments. Screening of all pregnant patients with robust treatment and follow-up represents the most effective method to reduce congenital syphilis currently available.

Reduced susceptibility to penicillin among pneumococci causing invasive infection in children - Canada, 1991 to 1998

PubMed Central

Scheifele, David; Halperin, Scott; Pelletier, Louise; Talbot, James; Lovgren, Marguerite; Vaudry, Wendy; Jadavji, Taj; Law, Barbara; MacDonald, Noni; Gold, Ron; Wang, Elaine; Mills, Elaine; Lebel, Marc; Déry, Pierre; Morris, Rob

2001-01-01

OBJECTIVE: To determine, over time, the rate and serotypes of pneumococci with reduced penicillin susceptibility obtained from children with invasive infection. DESIGN: Active, hospital-based, multicentre surveillance spanning from 1991 to 1998. SETTING: Eleven Canadian tertiary care paediatric facilities located from coast to coast. POPULATION STUDIED: 1847 children with invasive pneumococcal infection whose isolates (from a normally sterile site) were available for serotyping and standardized testing for penicillin susceptibility at the National Centre for Streptococcus. MAIN RESULTS: The prevalence of reduced penicillin susceptibility increased from 2.5% of 197 cases in 1991 to 13.0% of 276 cases in 1998. In the latter year, 8.7% of isolates had intermediate level resistance, and 4.3% had high level resistance. Since they were first detected in 1992, strains with high level resistance have been encountered only sporadically at most centres, but by 1998, all centres but two had encountered examples. Of 40 isolates with high level resistance and 101 isolates with intermediate level resistance, serotypes matched those included in new seven-valent conjugate vaccines for children in 97.5% and 79.2% of cases, respectively. CONCLUSIONS: Pneumococci with reduced susceptibility to penicillin are increasing in frequency across Canada among children with invasive infection. The Immunization Monitoring Program, Active data indicate that new conjugate vaccines could help to curb infections due to pneumococci with reduced susceptibility to penicillin but are unlikely to control completely the problem of antibiotic resistance. PMID:18159346

Comparison of antimicrobial susceptibilities of Corynebacterium species by broth microdilution and disk diffusion methods.

PubMed Central

Weiss, K; Laverdière, M; Rivest, R

1996-01-01

Corynebacterium species are increasingly being implicated in foreign-body infections and in immunocompromised-host infections. However, there are no specific recommendations on the method or the criteria to use in order to determine the in vitro activities of the antibiotics commonly used to treat Corynebacterium infections. The first aim of our study was to compare the susceptibilities of various species of Corynebacterium to vancomycin, erythromycin, and penicillin by using a broth microdilution method and a disk diffusion method. Second, the activity of penicillin against our isolates was assessed by using the interpretative criteria recommended by the National Committee for Clinical Laboratory Standards for the determination of the susceptibility of streptococci and Listeria monocytogenes to penicillin. Overall, 100% of the isolates were susceptible to vancomycin, while considerable variations in the activities of erythromycin and penicillin were noted for the different species tested, including the non-Corynebacterium jeikeium species. A good correlation in the susceptibilities of vancomycin and erythromycin between the disk diffusion and the microdilution methods was observed. However, a 5% rate of major or very major errors was detected with the Listeria criteria, while a high rate of minor errors (18%) was noted when the streptococcus criteria were used. Our findings indicate considerable variations in the activities of erythromycin and penicillin against the various species of Corynebacterium. Because of the absence of definite recommendations, important discrepancies were observed between the methods and the interpretations of the penicillin activity. PMID:8849254

Is gentamicin necessary in the antimicrobial treatment for group B streptococcal infections in the elderly? An in vitro study with human blood products.

PubMed

Ruppen, Corinne; Decosterd, Laurent; Sendi, Parham

2017-03-01

According to expert opinions, gentamicin should be administered as an adjunct to penicillin against severe group B streptococcal (GBS) infections. Whether the adjunct is important is of particular interest for elderly patients. Not only is the risk of aminoglycoside nephrotoxicity higher in elderly persons, but their immune defence to bacterial infections may also be impaired. Time-kill assays with human blood products, such as serum, neutrophilic granulocytes (opsonophagocytic assays) and whole blood from healthy, elderly volunteers were performed to evaluate the effect of gentamicin in combination with penicillin. In time-kill assays with human serum and in opsonophagocytic assays, we saw a trend for faster killing with the penicillin-gentamicin combination therapy. This effect was seen 4 and 6 h after antibiotic exposure but not at time points evaluated at ≥8 h. In whole blood killing assays, no difference in killing rates was observed with adjunctive gentamicin therapy. The criteria for synergism were not fulfilled when the effect of penicillin-gentamicin combinations was compared with that of penicillin monotherapy. Rapid killing of GBS within the first few hours was observed in time-kill assays with human blood products. Considering that elderly people are prone to gentamicin nephrotoxicity and that in severe GBS infection a high penicillin dose is administered every 4-6 h, the prolonged use of adjunctive aminoglycosides in these infections requires caution.

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

PubMed

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 0.87μgL(-1). Finally, the MIL-53-polymer was applied for the extraction of penicillin in river water and milk by spiking trace-level penicillin for as low as 50μgL(-1) and 100μgL(-1) with recoveries ranging from 80.8% to 90.9% (<6.7% RSDs) in river water and 81.1% to 100.7% (<7.1% RSDs) in milk sample, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Aminopenicillin-induced exanthema allows treatment with certain cephalosporins or phenoxymethyl penicillin.

PubMed

Trcka, Jiri; Seitz, Cornelia S; Bröcker, Eva-B; Gross, Gerd E; Trautmann, Axel

2007-07-01

Aminopenicillin-induced exanthema poses a problem in the management of infectious diseases. Due to theoretically possible immunological cross-reactivity, all beta-lactam drugs, i.e. penicillins, penicillin derivatives and cephalosporins, are usually avoided. The available alternative antibiotics (macrolides, quinolones and glycopeptides) may be less effective, have more side effects, and their use increases medical costs. Moreover, their use contributes to the increasing bacterial resistance to antibiotics. The aim of the study is to demonstrate that patients with aminopenicillin-induced exanthema may receive specific beta-lactams for future antibiotic therapy. Skin testing followed by oral challenges to identify beta-lactams that are tolerated by patients despite confirmed delayed-type non-immunoglobulin E (IgE)-mediated allergic hypersensitivity to aminopenicillins. Sixty-nine out of 71 patients (97.2%) with non-IgE-mediated allergic hypersensitivity to aminopenicillins tolerate cephalosporins without an aminobenzyl side chain such as cefpodoxime or cefixime and 51 patients (71.8%) also tolerate phenoxymethyl penicillin. The majority of patients with non-IgE-mediated allergic hypersensitivity to aminopenicillins do not cross-react to certain cephalosporins or phenoxymethyl penicillin. Skin and drug challenge tests can be helpful to determine individual cross-reactivity.

Anti-inflammatory and anti-oxidative effects of alpha-lipoic acid in experimentally induced acute otitis media.

PubMed

Tatar, A; Korkmaz, M; Yayla, M; Gozeler, M S; Mutlu, V; Halici, Z; Uslu, H; Korkmaz, H; Selli, J

2016-07-01

To investigate the anti-inflammatory, anti-oxidative and tissue protective effects, as well as the potential therapeutic role, of alpha-lipoic acid in experimentally induced acute otitis media. Twenty-five guinea pigs were assigned to one of five groups: a control (non-otitis) group, and otitis-induced groups treated with saline, penicillin G, alpha-lipoic acid, or alpha-lipoic acid plus penicillin G. Tissue samples were histologically analysed, and oxidative parameters in tissue samples were measured and compared between groups. The epithelial integrity was better preserved, and histological signs of inflammation and secretory metaplasia were decreased, in all groups compared to the saline treated otitis group. In the alpha-lipoic acid plus penicillin G treated otitis group, epithelial integrity was well preserved and histological findings of inflammation were significantly decreased compared to the saline, penicillin G and alpha-lipoic acid treated otitis groups. The most favourable oxidative parameters were observed in the control group, followed by the alpha-lipoic acid plus penicillin G treated otitis group. Alpha-lipoic acid, with its antioxidant, anti-inflammatory and tissue protective properties, may decrease the clinical sequelae and morbidity associated with acute otitis media.

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

NASA Astrophysics Data System (ADS)

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.

CELL DIVISION IN A SPECIES OF ERWINIA. III. REVERSAL OF INHIBITION OF CELL DIVISION CAUSED BY D-AMINO ACIDS, PENICILLIN, AND ULTRA-VIOLET LIGHT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grula, E.A.; Grula, M.M.

Inhibition of cell division in an Erwinia sp. occurs in the presence of any of six D-amino acids, penicillin, or ultraviolet light. Cell-division inhibition caused by D-amino acids is pH-dependent; however, elongation caused by penicillin occurs over a wide range of pH. Bulging and spheroplast formation in the presence of penicillin occurs only at pH values below 7.6; however, division continues to be inhibited at higher pH levels. Reversal of cell-division inhibition caused by two D-amino acids (phenylalanine and histidine) can be partially overcome by their respective L-isomers. Divalent cations (Zn, Ca, Mn) cause varying amounts of reversal of divisionmore » inhibition in all systems studied; each system appears to have an individual requirement. All induced division inhibitions, including that caused by penicillin, can be reversed by pantoyl lactone or omega methylpantoyl lactone. Evidence is presented and discussed concerning the possible importance of pantoyl lactone and divalent cations in terminal steps of the cell-division process in this organism. (auth)« less

21 CFR 558.58 - Amprolium and ethopabate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... slaughter Penicillin 2.4 to 50 For broiler chickens and replacement chickens where immunity to coccidiosis... pigmentation Not for laying hens; as procaine penicillin Roxarsone 22.7 to 45.4 (0.0025% to 0.005%) Broiler...

21 CFR 558.58 - Amprolium and ethopabate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... slaughter Penicillin 2.4 to 50 For broiler chickens and replacement chickens where immunity to coccidiosis... pigmentation Not for laying hens; as procaine penicillin Roxarsone 22.7 to 45.4 (0.0025% to 0.005%) Broiler...

21 CFR 558.58 - Amprolium and ethopabate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... slaughter Penicillin 2.4 to 50 For broiler chickens and replacement chickens where immunity to coccidiosis... pigmentation Not for laying hens; as procaine penicillin Roxarsone 22.7 to 45.4 (0.0025% to 0.005%) Broiler...

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

ERIC Educational Resources Information Center

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)

21 CFR 558.58 - Amprolium and ethopabate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... slaughter Penicillin 2.4 to 50 For broiler chickens and replacement chickens where immunity to coccidiosis... pigmentation Not for laying hens; as procaine penicillin Roxarsone 22.7 to 45.4 (0.0025% to 0.005%) Broiler...

One-Electron Reduction of Penicillins in Relation to the Oxidative Stress Phenomenon

PubMed Central

Szabó, László; Tóth, Tünde; Takács, Erzsébet; Wojnárovits, László

2015-01-01

Certain bactericidal antibiotics target mitochondrial components and, due to the leakage of electrons from the electron transport chain, one-electron reduction might occur that can lead to intermediates passing the electron to suitable acceptors. This study aimed at investigating the one-electron reduction mechanism of selected penicillin derivatives using pulse radiolysis techniques. Penicillins can accommodate the electron on each of their carbonyl carbon. Ketyl radicals are thus produced, which are reducing agents with possibility to interact with suitable biomolecules. A detailed mechanism of the reduction is reported. PMID:26690427

In vitro activity of gentamicin as an adjunct to penicillin against biofilm group B Streptococcus.

PubMed

Ruppen, Corinne; Hemphill, Andrew; Sendi, Parham

2017-02-01

Group B Streptococcus (GBS) increasingly causes invasive disease in non-pregnant adults, particularly in elderly persons and those with underlying diseases. Combination therapy with penicillin plus gentamicin has been suggested for periprosthetic joint infection. The postulated synergism of this combination is based on experiments with planktonic bacteria. We aimed to assess the efficacy of this combination against sessile bacteria. Four different GBS strains were used. We compared results of MICs with those of minimal biofilm eradication concentrations (MBECs), applied chequerboard assays to the MBEC device and calculated the fractional inhibitory concentration index. Synergism was evaluated with time-kill assays against bacteria adherent to cement beads, using penicillin (0.048, 0.2 and 3 mg/L), gentamicin (4 and 12.5 mg/L) and a combination thereof. Results were evaluated via colony counting after sonication of beads and scanning electron microscopy. MBEC/MIC ratios were 2000-4000 for penicillin and 1-4 for gentamicin. In chequerboard assays, synergism was observed in all four isolates. In time-kill assays, penicillin and 12.5 mg/L gentamicin showed synergism in two isolates. In the other two isolates 12.5 mg/L gentamicin alone was as efficient as the combination therapy. These in vitro investigations show activity of 12.5 mg/L gentamicin, alone or as an adjunct to penicillin, against four strains of biofilm GBS. This concentration cannot be achieved in bone with systemic administration, but can be reached if administered locally. The combination of systemic penicillin plus local gentamicin indicates a potential application in orthopaedic-device-associated GBS infections. Studies with a larger number of strains are required to confirm our results. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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 < .001). Seven adverse drug reactions occurred during guideline-driven test doses, with no significant difference in rate (3.9% vs 6.1%, P = .44) or severity (P > .5) between periods. Guideline-driven test doses decreased alternative antimicrobial therapy after the test dose, including vancomycin (68.3% vs 37.2%, P < .001), aztreonam (11.5% vs 0.5%, P < .001), aminoglycosides (6.0% vs 1.1%, P = .004), and fluoro quinolones (15.3% vs 3.3%, P < .001). The implementation of an inpatient antibiotic prescribing guideline for patients with 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.

Rationale behind high-dose amoxicillin therapy for acute otitis media due to penicillin-nonsusceptible pneumococci: support from in vitro pharmacodynamic studies.

PubMed Central

Lister, P D; Pong, A; Chartrand, S A; Sanders, C C

1997-01-01

To evaluate whether increased doses of amoxicillin should be used to treat acute pneumococcal otitis media, an in vitro pharmacokinetic model was used to evaluate the killing of pneumococci by amoxicillin when middle ear pharmacokinetics were simulated. Logarithmic-phase cultures were exposed to peak concentrations of 3, 6, and 9 microg of amoxicillin per ml every 12 h, and an elimination half-life of 1.6 h was simulated. Changes in viable bacterial counts were measured over 36 h. All three doses rapidly decreased the viable bacterial counts of penicillin-susceptible strains below the 10-CFU/ml limit of detection by 6 to 10 h and maintained counts below this limit through 36 h. The 3-microg/ml peak dose was much less effective against two of three strains with intermediate penicillin resistance and all three penicillin-resistant strains, with bacterial counts approaching those in drug-free control cultures by 12 h. The 6-microg/ml peak dose completely eliminated two of three strains with intermediate penicillin resistance and maintained viable counts of the other nonsusceptible strains at 1.5 to 2 logs below the initial inoculum through 36 h. The 9-microg/ml peak dose was most effective, completely eliminating all three strains with intermediate penicillin resistance and maintaining the viable counts of the resistant strains at 3 to 4 logs below the original inoculum. The pharmacodynamics observed in this study suggest that peak concentrations of amoxicillin of 6 to 9 microg/ml may be sufficient for the elimination of penicillin-nonsusceptible pneumococcal strains causing otitis media, especially those with intermediate resistance to amoxicillin. In vivo pharmacokinetic studies are needed to determine if these levels can be achieved in middle ear fluid with amoxicillin at 70 to 90 mg/kg/day divided into two daily doses. If these levels are reliably achieved, then clinical studies are warranted. PMID:9303386

The Molecular Structure of Penicillin

ERIC Educational Resources Information Center

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 CFR 113.28 - Detection of mycoplasma contamination.

Code of Federal Regulations, 2011 CFR

2011-01-01

... following: 1 percent tetrazolium chloride (ml) 5.5 1 percent thallium acetate (ml) 25 Penicillin (units) 500... solution 525,000 units of Penicillin. Dispense 10 ml aliquots into 60×15 mm disposable culture dishes or...

9 CFR 113.28 - Detection of mycoplasma contamination.

Code of Federal Regulations, 2013 CFR

2013-01-01

... following: 1 percent tetrazolium chloride (ml) 5.5 1 percent thallium acetate (ml) 25 Penicillin (units) 500... solution 525,000 units of Penicillin. Dispense 10 ml aliquots into 60×15 mm disposable culture dishes or...

9 CFR 113.28 - Detection of mycoplasma contamination.

Code of Federal Regulations, 2012 CFR

2012-01-01

... following: 1 percent tetrazolium chloride (ml) 5.5 1 percent thallium acetate (ml) 25 Penicillin (units) 500... solution 525,000 units of Penicillin. Dispense 10 ml aliquots into 60×15 mm disposable culture dishes or...

9 CFR 113.28 - Detection of mycoplasma contamination.

Code of Federal Regulations, 2014 CFR

2014-01-01

... following: 1 percent tetrazolium chloride (ml) 5.5 1 percent thallium acetate (ml) 25 Penicillin (units) 500... solution 525,000 units of Penicillin. Dispense 10 ml aliquots into 60×15 mm disposable culture dishes or...

Desensitization of anaphylactic hypersensitivity specific for the penicilloate minor determinant of penicillin and carbenicillin.

PubMed

Gorevic, P D; Levine, B B

1981-10-01

A 68-yr-old man with a history of a morbilliform rash caused by intravenous penicillin required carbenicillin (CB) therapy for refractory Serratia marcescens septicemia. Skin testing showed a positive immediate skin test to the penicilloate minor determinant in the presence of negative tests to benzylpenicilloylpolylysine (BPL) and penicillin G (PG), as well as cross-reactivity between the penicilloate derivatives of PG and CB. True densensitization was accomplished by gradual administration of CB intravenously and was accompanied by a diffuse flush reaction. There was specific loss of wheal-and-flare reactivity as well as of specific serum reaginic antibody activity during the procedure, and there was no evidence of activation of serum complement. This case illustrates the usefulness of skin tests in the prediction and management of penicillin allergy and presents data pertaining to immunologic mechanisms involved in true desensitization.

Serum Penicillin G Levels Are Lower Than Expected in Adults within Two Weeks of Administration of 1.2 Million Units

PubMed Central

Hansen, Christian J.; Russell, Kevin L.; Blumer, Jeffrey L.

2011-01-01

When introduced in the 1950s, benzathine penicillin G (BPG) was shown to be effective in eradicating group A beta-hemolytic streptococcus (GAS) for at least 3 weeks after administration. Several studies since the 1990s suggest that at 3–4 weeks serum penicillin G levels are less than adequate (below MIC90 of 0.016 µg/ml). We studied these levels for 4 weeks after the recommended dose of BPG in military recruits, for whom it is used as prophylaxis against GAS. The 329 subjects (mean age 20 years) each received 1.2 million units BPG IM and gave sera 1 day post injection and twice more at staggered time points over 4 weeks. Serum penicillin G levels were measured by liquid chromatography/tandem mass spectometry. The half-life of serum penicillin G was 4.1 days. By day 11, mean levels were <0.02 µg/ml, and by day 15<0.01 µg/ml. Levels in more than 50% of the subjects were below 0.02 µg/ml on day 9, and <.01 µg/ml on day 16. There was no demonstrable effect of subject body-surface area nor of the four different lots of BPG used. These data indicate that in healthy young adults serum penicillin G levels become less than protective <2½ weeks after injection of 1.2 million units of BPG. The findings require serious consideration in future medical and public health recommendations for treatment and prophylaxis of GAS upper respiratory tract infections. PMID:21991307

Interaction Between Low-Dose Methotrexate and Nonsteroidal Anti-inflammatory Drugs, Penicillins, and Proton Pump Inhibitors.

PubMed

Hall, Jill J; Bolina, Monika; Chatterley, Trish; Jamali, Fakhreddin

2017-02-01

To review the potential drug interactions between low-dose methotrexate (LD-MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs), penicillins, and proton-pump inhibitors (PPIs) given the disparity between interactions reported for high-dose and low-dose MTX to help guide clinicians. A literature search was performed in MEDLINE (1946 to September 2016), EMBASE (1974 to September 2016), and International Pharmaceutical Abstracts (1970 to January 2015) to identify reports describing potential drug interactions between LD-MTX and NSAIDS, penicillins, or PPIs. Reference lists of included articles were reviewed to find additional eligible articles. All English-language observational, randomized, and pharmacokinetic (PK) studies assessing LD-MTX interactions in humans were analyzed to determine clinical relevance in making recommendations to clinicians. Clinical case reports were assigned a Drug Interaction Probability Scale score. A total of 32 articles were included (28 with NSAIDs, 3 with penicillins, and 2 with PPIs [1 including both PPI and NSAID]). Although there are some PK data to describe increased LD-MTX concentrations when NSAIDs are used concomitantly, the clinical relevance remains unclear. Based on the limited data on LD-MTX with penicillins and PPIs, no clinically meaningful interaction was identified. Given the available evidence, the clinical importance of the interaction between LD-MTX and NSAIDs, penicillins, and PPIs cannot be substantiated. Health care providers should assess the benefit and risk of LD-MTX regardless of concomitant drug use, including factors known to predispose patients to MTX toxicity, and continue to monitor clinical and laboratory parameters per guideline recommendations.

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

PubMed

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.

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

PubMed Central

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. PMID:26267242

21 CFR 520.90c - Ampicillin trihydrate capsules.

Code of Federal Regulations, 2014 CFR

2014-04-01

... penicillinase-producing organisms and for use in animals known to be allergic to any of the penicillins. Not for...-producing organisms and for use in animals known to be allergic to any of the penicillins. Not for use in...

21 CFR 520.90c - Ampicillin trihydrate capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... penicillinase-producing organisms and for use in animals known to be allergic to any of the penicillins. Not for...-producing organisms and for use in animals known to be allergic to any of the penicillins. Not for use in...

21 CFR 520.90c - Ampicillin trihydrate capsules.

Code of Federal Regulations, 2012 CFR

2012-04-01

... penicillinase-producing organisms and for use in animals known to be allergic to any of the penicillins. Not for...-producing organisms and for use in animals known to be allergic to any of the penicillins. Not for use in...

21 CFR 520.90c - Ampicillin trihydrate capsules.

Code of Federal Regulations, 2013 CFR

2013-04-01

... penicillinase-producing organisms and for use in animals known to be allergic to any of the penicillins. Not for...-producing organisms and for use in animals known to be allergic to any of the penicillins. Not for use in...

21 CFR 520.90c - Ampicillin trihydrate capsules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... penicillinase-producing organisms and for use in animals known to be allergic to any of the penicillins. Not for...-producing organisms and for use in animals known to be allergic to any of the penicillins. Not for use in...

Key role of LaeA and velvet complex proteins on expression of β-lactam and PR-toxin genes in Penicillium chrysogenum: cross-talk regulation of secondary metabolite pathways.

PubMed

Martín, Juan F

2017-05-01

Penicillium chrysogenum is an excellent model fungus to study the molecular mechanisms of control of expression of secondary metabolite genes. A key global regulator of the biosynthesis of secondary metabolites is the LaeA protein that interacts with other components of the velvet complex (VelA, VelB, VelC, VosA). These components interact with LaeA and regulate expression of penicillin and PR-toxin biosynthetic genes in P. chrysogenum. Both LaeA and VelA are positive regulators of the penicillin and PR-toxin biosynthesis, whereas VelB acts as antagonist of the effect of LaeA and VelA. Silencing or deletion of the laeA gene has a strong negative effect on penicillin biosynthesis and overexpression of laeA increases penicillin production. Expression of the laeA gene is enhanced by the P. chrysogenum autoinducers 1,3 diaminopropane and spermidine. The PR-toxin gene cluster is very poorly expressed in P. chrysogenum under penicillin-production conditions (i.e. it is a near-silent gene cluster). Interestingly, the downregulation of expression of the PR-toxin gene cluster in the high producing strain P. chrysogenum DS17690 was associated with mutations in both the laeA and velA genes. Analysis of the laeA and velA encoding genes in this high penicillin producing strain revealed that both laeA and velA acquired important mutations during the strain improvement programs thus altering the ratio of different secondary metabolites (e.g. pigments, PR-toxin) synthesized in the high penicillin producing mutants when compared to the parental wild type strain. Cross-talk of different secondary metabolite pathways has also been found in various Penicillium spp.: P. chrysogenum mutants lacking the penicillin gene cluster produce increasing amounts of PR-toxin, and mutants of P. roqueforti silenced in the PR-toxin genes produce large amounts of mycophenolic acid. The LaeA-velvet complex mediated regulation and the pathway cross-talk phenomenon has great relevance for improving the production of novel secondary metabolites, particularly of those secondary metabolites which are produced in trace amounts encoded by silent or near-silent gene clusters.

Phenotypes and genes of resistance of pneumococci to penicillin isolated from children.

PubMed

Kotevska, V; Trajkovska-Dokic, E; Jankoska, G; Kaftandzieva, A; Panovski, N; Petrovska, M

2009-07-01

(Full text is available at http://www.manu.edu.mk/prilozi). In recent decades, the increase of Streptococcus pneumoniae strains resistant to beta-lactams, to other classes of antimicrobial drugs and especially to penicillin (penicillin-resistant pneumococcus - PRP) has further complicated the treatment of pneumococcal infection. Penicillin resistance in pneumococci is due to the development of altered penicillin-binding proteins (PBPs) in the bacterial cell wall. PBPs are known as six different variants (PBP1a, 1b, 2x, 2a, 2b and 3). to compare the presence and types of genes responsible for penicillin resistance in Streptococcus pneumoniae isolates with the minimal inhibitory concentrations (MIC) of penicillin as well as their correlation within the period of childhood. A total of 45 pneumococci obtained from nasal swabs and tracheal aspirates of children treated at the University Paediatric Clinic in Skopje were examined. According to age, the children were grouped as 1-3, 4-6 and 7-10 years. the oxacillin test (1microg) was used as a rapid screening test for the detection of PRP. MIC of penicillin were determined using the agar dilution method and interpreted according to NCCLS as resistant (if MIC are > 2 microg/ml), intermediate resistant (between 0,12-1.0 microg/ml) and susceptible (< 0,06 microg/ml). The genes pbp2b and pbp 2x, which are the genes mainly responsible for the onset of PRP, were detected using polymerase chain reaction (PCR). the oxacillin test showed that 38 pneumococci were resistant and 7 susceptible to penicillin. MIC of penicillin showed that 7 strains were resistant, 33 strains were intermediate resistant (12, 18, and 3 with MIC of 0.5 microg/ml, 0.25 microg/ml and 0.12 microg/ml, respectively) and 5 susceptible. According to MIC, of the total 40 resistant/intermediate resistant pneumococci, in 22 genes pbp2b and/or pbp2x, were confirmed (3 resistant strains with both genes; 7 intermediate resistant and 3 resistant strains with pbp2x genes; whereas 8 intermediate resistance and 1 susceptible strain with pbp2b). In a total of 11 strains (10 intermediate resistant and one resistant according to MIC), pbp2b and/or pbp2x genes were not detected, and their resistance is probably due to some other mechanisms or other genes that code PBP. The largest number of the examined pneumococci (32) were isolated from children aged 1-3 years and in 18 of them either pbp2b or pbp2x genes were detected. the oxacillin test is not suitable for discriminating the intermediate resistant and resistant pneumococci, while it is relevant for the detection of susceptible strains. Penicillin resistance of pneumococci that were causes of infection in children was on a lower level (15.5% resistant strains with MIC 1double dagger2 mg/ml and 73.3% intermediate resistant strains with MIC 0.12double dagger1 microg/ml). Pbp2b and/or pbp2x genes were detected in 22 of the examined strains and all of them except one were intermediate resistant or resistant. The Pbp2b gene is mostly present in the intermediate resistant strains and because it was detected in one susceptible strain, this gene is responsible for a low level of resistance. The pbp2x gene was detected in all the resistant strains and that is why we could conclude that it was coding the high level of resistance. Streptococcus pneumoniae was predominantly isolated from the age group 1-3 years where the PRP were not significant (Chi square; p > 0.05). Key words: Streptococcus pneumoniae, Penicillin resistance, Minimal Inhibitory Concentration (MIC), Genes of Resistance.

77 FR 20987 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Lincomycin Hydrochloride Soluble Powder...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-09

... Penicillin G powder. (a) Specifications. Each gram of powder contains penicillin G potassium equivalent to 1.... * * * * * (b) * * * (4) Nos. 054925, 057561, 061623, and 076475: 324 grams per pound as in paragraph (d) of...

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

PubMed

1988-06-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

The effect of /sup 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.

Investigation of β-lactam antibacterial drugs, β-lactamases, and penicillin-binding proteins with fluorescence polarization and anisotropy: a review

NASA Astrophysics Data System (ADS)

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.

HYPERSENSITIVITY TO PENICILLENIC ACID DERIVATIVES IN HUMAN BEINGS WITH PENICILLIN ALLERGY

PubMed Central

Parker, Charles W.; Shapiro, Jack; Kern, Milton; Eisen, Herman N.

1962-01-01

Multifunctional derivatives of penicillenic acid are effective elicitors of wheal-and-erythema skin responses in humans allergic to penicillin. Of the effective derivatives, penicilloyl-polylysines are particularly attractive as skin test reagents because they appear to be incapable of inducing antibody formation. The skin responses are specifically inhibitable in most instances by homologous unifunctional haptens. The penicillenic acid derivatives which appear to be determinants of human allergic reactions to penicillin are: penicilloyl, penicillenate, and groups of the penamaldate-penilloaldehyde type. Of these, the most significant appears to be the penicilloyl-lysyl determinant. PMID:14483916

Long-acting penicillins: historical perspectives.

PubMed

Markowitz, M

1985-01-01

For the more than three decades since benzathine penicillin G was discovered it remains unique as the only antibiotic formulation that can provide serum drug concentrations for several weeks following a single intramuscular injection. Benzathine penicillin G has withstood the test of time as the ideal drug to treat early, infectious syphilis and to prevent and treat Group A streptococcal infections. It has proved to be extraordinarily effective for the prevention of rheumatic fever recurrences and is a major reason for the marked reduction in the morbidity and mortality in countries where carefully monitored prophylaxis programs have been established.

Penicillin treatment accelerates middle ear inflammation in experimental pneumococcal otitis media.

PubMed Central

Kawana, M; Kawana, C; Giebink, G S

1992-01-01

Most Streptococcus pneumoniae strains are killed by very low concentrations of penicillin and other beta-lactam antibiotics, yet middle ear inflammation and effusion persist for days to weeks after treatment in most cases of pneumococcal otitis media. To study the effect of beta-lactam antibiotic treatment on pneumococci and the middle ear inflammatory response during pneumococcal otitis media, we measured concentrations of pneumococci, inflammatory cells, and lysozyme in middle ear fluid (MEF) by using the chinchilla model. Procaine penicillin G given intramuscularly 12 and 36 h after inoculation of pneumococci into the middle ear caused a significant acceleration in the MEF inflammatory cell concentration compared with that in untreated controls, with a significant peak in the inflammatory cell concentration 24 h after pneumococcal inoculation. The lysozyme concentration in MEF also increased more rapidly in treated than in control animals. Viable pneumococci were not detected in MEF after the second dose of penicillin, but the total pneumococcal cell concentration remained unchanged for at least 45 days. Therefore, penicillin treatment accelerated middle ear inflammation while killing pneumococci, but treatment did not accelerate clearance of the nonviable pneumococcal cells from MEF. Further studies will need to define the contribution of these responses to acute and chronic tissue injury. PMID:1563782

Relationships between skin test, specific IgE and levels of cytokines in patients with penicillin allergy.

PubMed

Qiao, H-L; Liu, J-H; Yang, J; Dong, Z-M

2005-08-01

The aim of this study was to investigate the relationships between skin test, specific immunoglobulin (Ig) E and cytokines in penicillin allergy. We collected the sera of 259 patients with historical positive skin test to penicillins, with immediate positive skin test and with a negative skin test results. The positive rate of specific IgE antibodies in 259 patients was 62.2% (161) by using radioallergosorbent test (RAST). Of the eight kinds of antigenic determinants, the positive rates of specific IgE to major and minor determinants were 43.63% (113) and 52.51% (136), respectively (p < 0.05). In 122 patients with immediate positive skin test, when the degrees of skin test were +, 2+, 3+ and 4+, the positive rates of specific IgE were 45.7, 57.1, 85.2 and 100%, respectively. The levels of interleukin (IL)-4, IL-13 and interferon (IFN)-gamma in the sera of patients with positive skin test were significantly increased with the degree of positive skin test (p < 0.05). The combined use of major and minor determinants in RAST offers the better test for the detection of penicillin-specific IgE antibodies. IL-4, IL-13 and IFN-gamma play important roles in penicillin allergy.

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

PubMed

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 < .001). Antimicrobial sensitivity testing was performed in 79.4% of cases (95% confidence interval, 68-87%), compared with 11.4% in 2004-2006 (P < .001). With directed intervention, adherence to the 2002 CDC guidelines for GBS prophylaxis in women who are allergic to penicillin improved dramatically. Copyright © 2011 Mosby, Inc. All rights reserved.

Penicillins and other acylamino compounds synthesized by the cell-bound penicillin acylase of Escherichia coli

PubMed Central

Cole, M.

1969-01-01

1. The penicillin acylase of Eschericha coli N.C.I.B. 8743 is a reversible enzyme. Reaction rates for the two directions have been determined. 2. Measurements of the rates of enzymic synthesis of penicillins from 6-aminopenicillanic acid and various carboxylic acids revealed that p-hydroxyphenylacetic acid was the best substrate, followed by phenylacetic, 2-thienylacetic, substituted phenylacetic, 3-hexenoic and n-hexanoic acids. 3. The rate of synthesis of penicillin improved when amides or N-acylglycines were used; α-aminobenzylpenicillin and phenoxymethylpenicillin were only synthesized when using these more energy-rich compounds. 4. Phenyl-acetylglycine was the best substrate for the synthesis of benzylpenicillin compared with other derivatives of phenylacetic acid. 5. The enzyme was specific for acyl-l-amino acids, benzylpenicillin being synthesized from phenylacetyl-l-α-aminophenylacetic acid but not from phenylacetyl-d-α-aminophenylacetic acid. 6. α-Phenoxyethylpenicillin was synthesized from 6-aminopenicillanic acid and α-phenoxypropionylthioglycollic acid non-enzymically, but the rate was faster in the presence of the enzyme. 7. The E. coli acylase catalysed the acylation of hydroxylamine by acids or amides to give hydroxamic acids, the phenylacetyl group being the most suitable acyl group. The enzyme also catalysed other acyl-group transfers. PMID:4982418

Management of allergy to penicillins and other beta-lactams.

PubMed

Mirakian, R; Leech, S C; Krishna, M T; Richter, A G; Huber, P A J; Farooque, S; Khan, N; Pirmohamed, M; Clark, A T; Nasser, S M

2015-02-01

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and non-immediate allergic reactions to penicillins and other beta-lactams. The guideline is intended for UK specialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, all BSACI members were consulted using a Web-based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta-lactams, molecular structure, formulations available in the UK and a description of known beta-lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross-reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta-lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included. © 2015 John Wiley & Sons Ltd.

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

PubMed

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.

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.

PubMed

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.

Inactivation of Penicillins by Thiol Broth

PubMed Central

Murray, Patrick R.; Niles, Ann C.

1982-01-01

Thiol broth with sodium polyanetholesulfonate inactivated penicillin G, carbenicillin, nafcillin, oxacillin, and gentamicin, but had no effect on cephalothin, cefoxitin, clindamycin, chloramphenicol, erythromycin, and tetracycline. Only Thiol broth was capable of this inactivation, which was not influenced by the presence of blood. PMID:7153352

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

PubMed

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 < 0.05). Compliance with treatment was 94 and 98 %, respectively. Adverse events were reported in 14 % with both regimens (all mild). (2) Second-line treatment: Intention-to-treat eradication rate with omeprazole-clarithromycin-levofloxacin was 64 % both after triple and quadruple 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.

Structural Effect of the Asp345a Insertion in Penicillin-Binding Protein 2 from Penicillin-Resistant Strains of Neisseria gonorrhoeae

PubMed Central

2015-01-01

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. PMID:25403720