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Radiation and Environmental Biophysics Mar 2014The aim of this work was to determine the concentrations and properties of free radicals in piperacillin, ampicillin, and crystalline penicillin after gamma irradiation....
The aim of this work was to determine the concentrations and properties of free radicals in piperacillin, ampicillin, and crystalline penicillin after gamma irradiation. The radicals were studied by electron paramagnetic resonance (EPR) spectroscopy using an X-band spectrometer (9.3 GHz). Gamma irradiation was performed at a dose of 25 kGy. One- and two-exponential functions were fitted to the experimental data, in order to assess the influence of the antibiotics' storage time on the measured EPR lines. After gamma irradiation, complex EPR lines were recorded confirming the presence of a large number of free radicals formed during the irradiation. For all tested antibiotics, concentrations of free radicals and parameters of EPR spectra changed with storage time. The results obtained demonstrate that concentration of free radicals and other spectroscopic parameters can be used to select the optimal parameters of radiation sterilization of β-lactam antibiotics. The most important parameters are the constants τ (τ (1(A),(I)) and τ (2(A),(I))) and K (K (0(A),(I)), K (1(A),(I)), K (2(A),(I))) of the exponential functions that describe free radicals decay during samples storage.
Topics: Ampicillin; Anti-Bacterial Agents; Free Radicals; Gamma Rays; Microscopy, Energy-Filtering Transmission Electron; Penicillins; Piperacillin; Sterilization
PubMed: 24213588
DOI: 10.1007/s00411-013-0498-1 -
California Medicine Sep 1962The newer penicillins give high promise of overcoming some of the few disadvantages of penicillin-G. THEY FALL INTO THREE GROUPS: The alpha-phenoxy-penicillins; the...
The newer penicillins give high promise of overcoming some of the few disadvantages of penicillin-G. THEY FALL INTO THREE GROUPS: The alpha-phenoxy-penicillins; the penicillinase resistant penicillins; and the penicillins with enhanced activity against gram-negative bacteria. The newer alpha-phenoxy-penicillins offer little over alpha-phenoxy methyl penicillin (penicillin-V). As the length of the side chain is increased, absorption and attainable serum concentration is also increased, but these are questionable benefits and probably not significant for therapeusis. The penicillinase-resistant penicillins have once more brought almost all severe staphylococcal infections within therapeutic range. One of them, methicillin, must be administered parenterally. It is the agent of choice for the treatment of severe, penicillin-G resistant staphylococcal infections, and this is its only clinical indication. Another, oxacillin, which may be administered orally, is partially resistant to gastric acid degradation, but must be given on an empty stomach. It is most useful as prolonged therapy following methicillin, in the treatment of mixed hemolytic streptococcal-penicillin-G resistant staphylococcal infections, and as primary therapy for moderately severe penicillin-G resistant staphylococcal infections. The third group is still mostly in the experimental stage, but some strains of Proteus, E. coli, Salmonella and Shigella are highly vulnerable to their action. Toxic and allergic reactions to the newer penicillins, and crossed allergic reactions with penicillin-G, present unsolved problems.
Topics: Escherichia coli; Methicillin; Oxacillin; Penicillin G; Penicillins; Staphylococcal Infections; Staphylococcus; Streptococcal Infections
PubMed: 13913108
DOI: No ID Found -
British Medical Journal Sep 1971
Topics: Administration, Oral; Adult; Cloxacillin; Convalescence; Erythromycin; Humans; Injections, Intramuscular; Male; Middle Aged; Penicillin G; Penicillins; Pneumonia; Pneumonia, Pneumococcal; Smoking; Staphylococcus; Streptococcus pneumoniae
PubMed: 4399404
DOI: No ID Found -
Journal of Clinical Pathology Apr 1977Thirty-four recent clinical isolates of Streptococcus faecalis were tested for sensitivity to amoxycillin, benzylpenicillin, streptomycin, kanamycin, gentamicin,...
Thirty-four recent clinical isolates of Streptococcus faecalis were tested for sensitivity to amoxycillin, benzylpenicillin, streptomycin, kanamycin, gentamicin, tobramycin, and amikacin. Amoxycillin was two- to four-fold more active than benzylpenicillin and all strains were inhibited by low concentrations of the penicillins. The aminoglycosides were less active against the enterococci than were the penicillins and a significant number of strains were insensitive or relatively insensitive to one or more of the aminoglycosides. Thus, eight (23%) strains showed a high level of resistance to streptomycin and kanamycin (MIC greater 5000 microng/ml) but were sensitive to gentamicin, tobramycin, and amikacin. In addition, two strains of Strep. faecalis, isolated at different hospitals from patients who had received topical gentamicin therapy, were relatively resistant to gentamicin (MIC250 to 500 microng/ml) and were less sensitive also to the other aminoglycosides. Bactericidal synergy was demonstrated by amoxycillin/aminoglycoside combinations against the enterococci, provided that the test strain of Strep. faecalis was sensitive to the aminoglycoside in the combination. An exception to this was the combination of amoxycillin plus amikacin which was not synergistic against kanamycin-resistant strains of Strep. faecalis although these organisms were sensitive to amikacin in the growth inhibition tests. The gentamicin-resistant strains showed variable responses to amoxycillin/aminoglycoside combinations in tests for bactericidal synergy and were generally less sensitive than typical strains of Strep. faecalis.
Topics: Aminoglycosides; Amoxicillin; Drug Evaluation; Drug Synergism; Enterococcus faecalis; Gentamicins; Humans; Kanamycin; Microbial Sensitivity Tests; Penicillin G; Penicillin Resistance; Streptomycin; Tobramycin
PubMed: 404337
DOI: 10.1136/jcp.30.4.375 -
CMAJ : Canadian Medical Association... Jun 1986Although penicillin is nontoxic, it is highly immunogenic and is the most common drug that causes allergic reactions. A previous reaction to penicillin has been shown to... (Review)
Review
Although penicillin is nontoxic, it is highly immunogenic and is the most common drug that causes allergic reactions. A previous reaction to penicillin has been shown to be unreliable in predicting sensitivity in 75% to 90% of patients. To more accurately test for penicillin allergy, diagnostic skin test reagents have been developed; these include the major determinant (benzylpenicilloyl-polylysine) and the minor determinant mixture (penicillin G potassium, benzylpenicilloate sodium and benzylpenicilloyl-N-propylamine). Penicillin skin testing has been shown to be safe and useful in predicting immediate IgE-mediated reactions (overall predictive value 99%). Reactions that occur when patients are challenged with penicillin are mild or accelerated urticarial reactions. We outline a practical and rational therapeutic approach based on the current understanding of penicillin allergy.
Topics: Desensitization, Immunologic; Drug Hypersensitivity; False Negative Reactions; Humans; Indicators and Reagents; Penicillin G; Penicillins; Skin Tests
PubMed: 3518897
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Aug 2017Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a...
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.
Topics: Adult; Aged; Anti-Bacterial Agents; Dried Blood Spot Testing; Female; Humans; Injections, Intramuscular; Limit of Detection; Male; Middle Aged; Penicillin G; Penicillin G Benzathine; Rheumatic Fever; Rheumatic Heart Disease
PubMed: 28559267
DOI: 10.1128/AAC.00252-17 -
The Journal of Antimicrobial... Jun 2022Acute rheumatic fever (ARF), an autoimmune reaction to Group A Streptococcus (Streptococcus pyogenes; Strep A) infection, can cause rheumatic heart disease (RHD). New...
BACKGROUND
Acute rheumatic fever (ARF), an autoimmune reaction to Group A Streptococcus (Streptococcus pyogenes; Strep A) infection, can cause rheumatic heart disease (RHD). New formulations of long-acting penicillins are being developed for secondary prophylaxis of ARF and RHD.
OBJECTIVES
To evaluate the penicillin G concentrations required to suppress growth of Strep A.
METHODS
Broth microdilution MIC and MBC for Strep A strains M75611024, M1T15448 and M18MGAS8232 were determined. All strains were studied in a hollow fibre model (initial inoculum 4 log10 cfu/mL). Constant penicillin G concentrations of 0.008, 0.016 and 0.05 mg/L were examined against all strains, plus 0.012 mg/L against M18MGAS8232. Viable counts were determined over 144 h. Subsequently, all penicillin G-treated cartridges were emptied, reinoculated with 5 log10 cfu/mL and counts determined over a further 144 h. Mathematical modelling was performed.
RESULTS
MIC and MBC were 0.008 mg/L for all strains; small subpopulations of M75611024 and M1T15448, but not M18MGAS8232, grew at 1× MIC. Following the first inoculation, 0.008 mg/L achieved limited killing and/or stasis against M75611024 and M1T15448, with subsequent growth to ∼6 log10 cfu/mL. Following both inocula, concentrations ≥0.016 mg/L suppressed M75611024 and M1T15448 to <1 log10 cfu/mL from 6 h onwards with eradication. Concentrations ≥0.008 mg/L suppressed M18MGAS8232 to <1 log10 cfu/mL from 24 h onwards with eradication after both inoculations. Mathematical modelling well described all strains using a single set of parameter estimates, except for different maximum bacterial concentrations and proportions of bacteria growing at 1× MIC.
CONCLUSIONS
In the absence of validated animal and human challenge models, the study provides guidance on penicillin G target concentrations for development of new penicillin formulations.
Topics: Animals; Anti-Bacterial Agents; Microbial Sensitivity Tests; Penicillin G; Penicillins; Streptococcal Infections; Streptococcus pyogenes
PubMed: 35470370
DOI: 10.1093/jac/dkac124 -
The Journal of Antimicrobial... May 2020Staphylococcus lugdunensis belongs to the CoNS group, but is regarded to be more virulent than most other CoNS. It is also remarkably susceptible to antibiotics,...
BACKGROUND
Staphylococcus lugdunensis belongs to the CoNS group, but is regarded to be more virulent than most other CoNS. It is also remarkably susceptible to antibiotics, including penicillin G.
OBJECTIVES
To evaluate different methods for penicillin susceptibility testing, to assess penicillin susceptibility rates among S. lugdunensis and to describe the clinical presentation including antibiotic treatment.
METHODS
Clinical isolates of S. lugdunensis were tested for penicillin susceptibility using disc diffusion according to CLSI (10 U disc) and EUCAST (1 U disc), assessment of zone-edge appearance, nitrocefin test and Etest for MIC determination. PCR of the blaZ gene was used as a reference method.
RESULTS
Of the 112 isolates included in the study, 67% were susceptible to penicillin G according to blaZ PCR. The EUCAST disc diffusion test had 100% sensitivity, whereas the CLSI method had one very major error with a false-susceptible isolate. When zone-edge appearance was included in the assessment, the false-susceptible isolate was correctly classified as resistant. Foreign-body infection was the most common focus of infection, affecting 49% of the participants. Only 4% of the patients were treated with penicillin G.
CONCLUSIONS
Penicillin susceptibility is common in S. lugdunensis and the disc diffusion method according to EUCAST had a higher sensitivity than that of CLSI. Assessment of zone-edge appearance could increase the sensitivity of the disc diffusion test. Penicillin susceptibility testing and treatment should be considered in S. lugdunensis infections.
Topics: Anti-Bacterial Agents; Disk Diffusion Antimicrobial Tests; Humans; Microbial Sensitivity Tests; Penicillin G; Penicillins; Staphylococcus lugdunensis
PubMed: 32016343
DOI: 10.1093/jac/dkaa004 -
European Journal of Clinical... Aug 2019Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) with unusual pathogenicity resembling that of S. aureus. Unlike other CoNS, S. lugdunensis...
Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) with unusual pathogenicity resembling that of S. aureus. Unlike other CoNS, S. lugdunensis remains susceptible to most antibiotics. The resistance to penicillin varies widely (range, 15-87% worldwide), whereas methicillin resistance is still rare. We aimed to evaluate treatment options for infections caused by S. lugdunensis and more specifically to investigate whether penicillin G could be a better treatment choice than oxacillin. Susceptibility testing was performed using the disc diffusion method for penicillin G, cefoxitin, trimethoprim/sulfamethoxazole, erythromycin, clindamycin, gentamicin, norfloxacin, fusidic acid, rifampicin, and fosfomycin. Isolates susceptible to penicillin G were further tested with a gradient test for penicillin G and oxacillin. Of the 540 clinical isolates tested, 74.6% were susceptible to penicillin G. Among these penicillin-susceptible isolates, the MIC and MIC values for penicillin G were threefold lower than that for oxacillin. A majority of the isolates were susceptible to all other antibiotics tested. Breakpoints for fosfomycin have not yet been defined, and so no conclusions could be drawn. Two isolates were resistant to cefoxitin and carried the mecA gene; whole-genome sequencing revealed that both harbored the SCCmec element type IVa(2B). S. lugdunensis isolated in Sweden were susceptible to most tested antibiotics. Penicillin G may be a more optimal treatment choice than oxacillin. Although carriage of the mecA gene is rare among S. lugdunensis, it does occur.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Oxacillin; Penicillin G; Staphylococcus lugdunensis; Sweden; Whole Genome Sequencing
PubMed: 31144243
DOI: 10.1007/s10096-019-03571-6 -
American Journal of Veterinary Research Jul 2000To compare the pharmacokinetics of penicillin G and procaine in racehorses following i.m. administration of penicillin G procaine (PGP) with pharmacokinetics following... (Comparative Study)
Comparative Study
OBJECTIVE
To compare the pharmacokinetics of penicillin G and procaine in racehorses following i.m. administration of penicillin G procaine (PGP) with pharmacokinetics following i.m. administration of penicillin G potassium and procaine hydrochloride (PH).
ANIMALS
6 healthy adult mares.
PROCEDURE
Horses were treated with PGP (22,000 units of penicillin G/kg of body weight, i.m.) and with penicillin G potassium (22,000 U/kg, i.m.) and PH (1.55 mg/kg, i.m.). A minimum of 3 weeks was allowed to elapse between drug treatments. Plasma and urine penicillin G and procaine concentrations were measured by use of high-pressure liquid chromatography.
RESULTS
Median elimination phase half-lives of penicillin G were 24.7 and 12.9 hours, respectively, after administration of PGP and penicillin G potassium. Plasma penicillin G concentration 24 hours after administration of penicillin G potassium and PH was not significantly different from concentration 24 hours after administration of PGP. Median elimination phase half-life of procaine following administration of PGP (15.6 hours) was significantly longer than value obtained after administration of penicillin G potassium and PH (1 hour).
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggest that i.m. administration of penicillin G potassium will result in plasma penicillin G concentrations for 24 hours after drug administration comparable to those obtained with administration of PGP Clearance of procaine from plasma following administration of penicillin G potassium and PH was rapid, compared with clearance following administration of PGP.
Topics: Animals; Area Under Curve; Chromatography, High Pressure Liquid; Female; Half-Life; Horses; Injections, Intramuscular; Least-Squares Analysis; Penicillin G Procaine; Penicillins; Statistics, Nonparametric
PubMed: 10895905
DOI: 10.2460/ajvr.2000.61.811