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Antimicrobial Agents and Chemotherapy Jul 1996Previous time-kill studies have shown that RP 59500 is rapidly bactericidal against pneumococci. To extend these findings, the activities of RP 59500, its two components... (Comparative Study)
Comparative Study
Previous time-kill studies have shown that RP 59500 is rapidly bactericidal against pneumococci. To extend these findings, the activities of RP 59500, its two components RP 57669 RP 54476, penicillin G, erythromycin and sparfloxacin against 26 penicillin-susceptible, 25 penicillin-intermediate, and 25 penicillin-intermediate, and 25 penicillin-resistant pneumococci were determined by the agar dilution MIC and the time-kill testing methodologies within 10 min (ca. 0.2 h) and at 1 and 2 h. Respective agar dilution MICs at which 90% of isolates are inhibited for penicillin-susceptible, -intermediate, and -resistant strains were as follows: penicillin G, 0.03, 1, and 4 micrograms/ml;RP 59500, 1, 1, and 1 microgram/ml; RP 57669, 8, 32, and 16 micrograms/ml; RP 54476, > 128, > 128, and > 128 micrograms/ml; erythromycin, 0.06, 2, and > 128 micrograms/ml; and sparfloxacin, 1, 0.5, and 0.5 microgram/ml. RP 59500 was equally active (MIC at which 90% of isolates are inhibited, 1.0 microgram/ml) against erythromycin-susceptible and -resistant strains. Time-kill testing results showed that only RP 59500 at one to four times the MIC killed pneumococci at 0.2 h; RP 59500 was also the most active compound at 1 and 2 h. By comparison, penicillin and sparfloxacin at one, two, and four times the MICs reduced the original inoculum by > or = 1 log at 2 h for 46, 80, and 95% and for 50, 72, and 86% of strains, respectively. The killing activity of RP 59500 was the same against erythromycin-susceptible and -resistant strains. RP 57669, RP 54479, and erythromycin were either inactive or bacteriostatic at 2 h. Of all drugs tested, RP 59500 yielded the most rapid killing.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Erythromycin; Fluoroquinolones; Microbial Sensitivity Tests; Penicillin G; Penicillin Resistance; Penicillins; Quinolones; Streptococcus pneumoniae; Time Factors; Virginiamycin
PubMed: 8807057
DOI: 10.1128/AAC.40.7.1653 -
European Journal of Biochemistry Sep 1980Streptococcus faecalis ATCC 9790 possesses seven membrane-bound penicillin-binding proteins. They have been characterized with respect to their apparent molecular...
Streptococcus faecalis ATCC 9790 possesses seven membrane-bound penicillin-binding proteins. They have been characterized with respect to their apparent molecular weights, relative abundance, specificity profiles for 15 different beta-lactam antibiotics and stability under various conditions. In water and at 37 degrees C, all the native penicillin-binding proteins have half-lives longer than 20 h except protein 3b (half-life of about 600 min) and protein 4 (half-life of about 175 min). The short-lived 80 000-Mr protein 4 is spontaneously converted into a 73 000-Mr water-soluble, penicillin-binding protein 4. Similarly, the short-lived 82 000-Mr protein 3b seems to be the protein from which the 72 000-Mr water-soluble protein X spontaneously originates during incubation of the membranes. Release of both proteins 4 and X from the membrane is maximal under alkaline conditions; it is not inhibited by various protease inhibitors. After exposure to trypsin, the 43 000-Mr membrane-bound penicillin binding protein 6 (a DD-carboxypeptidase) gives to a 30 000-Mr water-soluble protein 6. Like the parent protein, protein 6 exhibits both DD-carboxypeptidase activity and penicillin-binding ability. With proteins 6 and 6, low dose levels of p-chloromercuribenzoate prevent both enzyme activity and combination with penicillin, thus strongly suggesting that a thiol group is involved in the enzyme active center. We have shown previously [Coyette et al. in Eur. J. Biochem. 88, 297--305 (1978) and 75, 231--239 (1977)] that the DD-carboxypeptidase protein 6 fragments the benzylpenicillin molecule with formation of phenylacetylglycine. Breakdown of the complex formed between [14C]benzylpenicillin and 14 000-Mr membrane-bound protein 1 is also 'enzyme-catalysed'. Most likely, however, the released product is penicilloate. With all the other penicillin-binding proteins whose molecular weights are intermediate between those of proteins 1 and 6, breakdown of the complexes formed with [14C]benzylpenicillin results from proteolysis and is not due to the release of the bound metabolite. None of the penicillin-binding proteins behaves, by itself, as a lethal target for beta-lactam antibiotic action on the living cells.
Topics: Binding, Competitive; Carrier Proteins; Cell Membrane; Enterococcus faecalis; Half-Life; Kinetics; Molecular Weight; Muramoylpentapeptide Carboxypeptidase; Penicillin G; Penicillins
PubMed: 6777159
DOI: 10.1111/j.1432-1033.1980.tb04886.x -
BMJ Open Dec 2022Regular intramuscular benzathine penicillin G injections have been the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis since the 1950s. As the...
Study protocol for controlled human infection for penicillin G against : a double-blinded, placebo-controlled, randomised trial to determine the minimum concentration required to prevent experimental pharyngitis (the CHIPS trial).
INTRODUCTION
Regular intramuscular benzathine penicillin G injections have been the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis since the 1950s. As the pharmacological correlate of protection remains unknown, it is difficult to recommend changes to this established regimen. Determining the minimum effective penicillin exposure required to prevent infection will accelerate development of new long-acting penicillins for RHD prevention as well as inform opportunities to improve existing regimens. The CHIPS trial will address this knowledge gap by directly testing protection afforded by different steady state plasma concentrations of penicillin in an established model of experimental human pharyngitis.
METHODS AND ANALYSIS
This is a double-blinded, placebo-controlled, randomised experimental human infection study. Sixty healthy adult volunteers aged 18-40 years will be recruited and randomised 1:1:1:1:1 to continuous intravenous penicillin infusions targeting five different steady state plasma concentrations of 0 (placebo), 3, 6, 12 and 20 ng/mL via a midline catheter. Each participant's penicillin pharmacokinetic parameters will be established prior to the challenge, to ensure accurate dosing for the continuous infusion. Following the challenge with a well-characterised strain of , participants will be observed for up to 6 days for the development of pharyngitis and treated with antibiotics prior to discharge. The primary objective is to determine the minimum effective steady-state plasma penicillin concentration required to prevent experimental pharyngitis. Secondary objectives will explore systemic and mucosal immunoinflammatory responses during pharyngitis, bacterial colonisation dynamics, environmental contamination and qualitative evaluation of the participant experience.
ETHICS AND DISSEMINATION
Ethical approval has been obtained (Bellberry Human Research Ethics Committee). Findings will be reported in peer-reviewed publications and presented at national/international stakeholder forums.
TRIAL REGISTRATION NUMBER
ACTRN12621000751875.
Topics: Adult; Humans; Streptococcus pyogenes; Penicillin G; Pharyngitis; Anti-Bacterial Agents; Penicillin G Benzathine; Streptococcal Infections; Randomized Controlled Trials as Topic
PubMed: 36600395
DOI: 10.1136/bmjopen-2022-064022 -
Journal of Clinical Pathology Sep 1970
Topics: Ampicillin; Enterobacteriaceae; Microbial Sensitivity Tests; Penicillin G
PubMed: 5476884
DOI: 10.1136/jcp.23.6.552-a -
British Medical Journal Aug 1978
Topics: Cloxacillin; Drug Therapy, Combination; Gentamicins; Humans; Penicillin G; Sepsis
PubMed: 698577
DOI: No ID Found -
Journal of Chromatography. A Nov 2021The presence of antibiotics in the aquatic environment is becoming one of the main research focus of scientists and policy makers. Proof of that is the inclusion of four...
The presence of antibiotics in the aquatic environment is becoming one of the main research focus of scientists and policy makers. Proof of that is the inclusion of four antibiotics, amongst which is amoxicillin, in the EU Watch List (WL) (Decision 2020/1161/EU)) of substances for water monitoring. The accurate quantification of amoxicillin in water at the sub-ppb levels required by the WL is troublesome due to its physicochemical properties. In this work, the analytical challenges related to the determination of amoxicillin, and six related penicillins (ampicillin, cloxacillin, dicloxacillin, penicillin G, penicillin V and oxacillin), have been carefully addressed, including sample treatment, sample stability, chromatographic analysis and mass spectrometric detection by triple quadrupole. Given the low recoveries obtained using different solid-phase extraction cartridges, we applied the direct injection of water samples using a reversed-phase chromatographic column that allowed working with 100% aqueous mobile phase. Matrix effects were evaluated and corrected using the isotopically labelled internal standard or correction factors based on signal suppression observed in the analysis of spiked samples. The methodology developed was satisfactorily validated at 50 and 500 ng L for the seven penicillins studied, and it was applied to different types of water matrices, revealing the presence of ampicillin in one surface water sample and cloxacillin in three effluent wastewater samples.
Topics: Amoxicillin; Ampicillin; Chromatography, High Pressure Liquid; European Union; Penicillins; Solid Phase Extraction; Water
PubMed: 34662823
DOI: 10.1016/j.chroma.2021.462605 -
PloS One 2015Antibiotics, such as benzyl-penicillin (PenG) and cephalosporin, are the most common compounds used in animal therapy. Their massive and illegal use in animal therapy...
Antibiotics, such as benzyl-penicillin (PenG) and cephalosporin, are the most common compounds used in animal therapy. Their massive and illegal use in animal therapy and prophylaxis inevitably causes the presence of traces in foods of animal origin (milk and meat), which creates several problems for human health. With the aim to prevent the negative impact of β-lactam and, in particular, PenG residues present in the milk on customer health, many countries have established maximum residue limits (MRLs). To cope with this problem here, we propose an effective alternative, compared to the analytical methods actually employed, to quantify the presence of penicillin G using the surface plasmon resonance (SPR) method. In particular, the PenG molecule was conjugated to a protein carrier to immunize a rabbit and produce polyclonal antibodies (anti-PenG). The produced antibodies were used as molecular recognition elements for the design of a competitive immune-assay for the detection of PenG by SPR experiments. The detection limit of the developed assay was found to be 8.0 pM, a value much lower than the MRL of the EU regulation limit that is fixed at 12 nM. Thus, our results clearly show that this system could be successfully suitable for the accurate and easy determination of PenG.
Topics: Animals; Anti-Bacterial Agents; Antibodies; Chromatography, Affinity; Drug Residues; Enzyme-Linked Immunosorbent Assay; Limit of Detection; Milk; Penicillin G; Surface Plasmon Resonance
PubMed: 26168259
DOI: 10.1371/journal.pone.0132396 -
Antimicrobial Agents and Chemotherapy Dec 1981The in vitro activity of mezlocillin was compared to penicillin G, ampicillin, carbenicillin, and ticarcillin in tests with 195 gram-positive bacteria and 20 Haemophilus... (Comparative Study)
Comparative Study
The in vitro activity of mezlocillin was compared to penicillin G, ampicillin, carbenicillin, and ticarcillin in tests with 195 gram-positive bacteria and 20 Haemophilus influenzae. Against gram-positive isolates excluding enterococci, penicillin was the most active drug, followed by ampicillin, mezlocillin, carbenicillin, and ticarcillin. Ampicillin was the most active of the five drugs against enterococci, whereas mezlocillin was the most active drug against 14 strains of ampicillin-susceptible H. influenzae.
Topics: Ampicillin; Bacteria; Carbenicillin; Haemophilus influenzae; Mezlocillin; Penicillin G; Penicillins; Ticarcillin
PubMed: 6459766
DOI: 10.1128/AAC.20.6.843 -
Emerging Infectious Diseases May 2017There is no proven alternative to penicillin for treatment of maternal syphilis. We report 2 case-patients with maternal syphilis who were successfully treated without...
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.
Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Ceftriaxone; Drug Substitution; Female; Humans; Infant, Newborn; Penicillin G Benzathine; Penicillins; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Syphilis; Treatment Outcome; Young Adult
PubMed: 28418316
DOI: 10.3201/eid2305.161936 -
Canadian Journal of Comparative... Apr 1975The effect of oral and parenteral penicillin on the development of cellular and humoral immune responses in chimpanzees infected with group A streptococcal M-types 1, 5...
The effect of oral and parenteral penicillin on the development of cellular and humoral immune responses in chimpanzees infected with group A streptococcal M-types 1, 5 and 12 was investigated. The interrelationship between type-specific antibody response and enhancement of phagocytic competence of polymorphonuclear neutrophils was documented. Penicillin depressed or suppressed type-specific antibody response depending on the mode and dose of administration, probably because of its effect on the streptococci responsible for antibody stimulation. Penicillin was not demonstrated to have a direct effect on phagocytic ability in vitro. Therefore the primary effect of antibiotic therapy is the indirect relationship to suppression or inhibition of type-specific antibody response to M-protein which results in a diminution of phagocytic competence.
Topics: Administration, Oral; Animals; Antibodies, Bacterial; Antibody Formation; Hemagglutination Tests; Pan troglodytes; Penicillin G Benzathine; Penicillin V; Penicillins; Phagocytosis; Pharyngitis; Streptococcal Infections; Streptococcus
PubMed: 804981
DOI: No ID Found