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Bulletin of the World Health... 1956Post-treatment observation of two years' duration has confirmed preliminary data which indicated that a single injection of 2.5 million units of benzathine penicillin G,...
Post-treatment observation of two years' duration has confirmed preliminary data which indicated that a single injection of 2.5 million units of benzathine penicillin G, in early infectious syphilis, produces results equal, if not superior, to those obtained with schedules employing 4.8 million units of procaine penicillin and aluminium monostearate.Preliminary data suggest that a single injection of 2.4 or 2.5 million units of benzathine penicillin G may be inadequate for the treatment of asymptomatic neurosyphilis.Delayed reactions do not appear to be induced by the long-sustained blood-levels following the administration of benzathine penicillin G.Repeated injections of PAM increase the risk of reaction to treatment.
Topics: Communicable Diseases; Humans; Penicillin G Benzathine; Penicillins; Stearic Acids; Syphilis
PubMed: 13404473
DOI: No ID Found -
The Journal of Antibiotics Dec 1978The affinities of cefoxitin, a cephamycin antibiotic, to penicillin-binding proteins of Escherichia coli were reexamined using a recently developed method for separating...
Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli.
The affinities of cefoxitin, a cephamycin antibiotic, to penicillin-binding proteins of Escherichia coli were reexamined using a recently developed method for separating penicillin-binding proteins. The inhibitions by this antibiotic of four measurable penicillin-sensitive enzymatic reactions, the reactions of D-alanine carboxypeptidases IA and IB, cross-bridge formation and concomitant release of D-alanine, were also measured. An approximate correlation was found between the affinities of cefoxitin to the penicillin-binding proteins responsible for these reactions and its rates of inhibition of the respective penicillin-sensitive reactions.
Topics: Bacterial Proteins; Binding, Competitive; Carrier Proteins; Cefoxitin; Cephalosporins; Escherichia coli; Penicillin G; Penicillins; Protein Binding
PubMed: 368000
DOI: 10.7164/antibiotics.31.1292 -
Acta Veterinaria Scandinavica 1986The penetration of penicillin into tissue cage fluid (TCF) in calves was studied after intravenous and intramuscular injection. The penicillin concentrations in TCF were...
The penetration of penicillin into tissue cage fluid (TCF) in calves was studied after intravenous and intramuscular injection. The penicillin concentrations in TCF were lower than in serum and maximum was reached much later. Intravenous injection of benzyl-penicillin gave significantly higher levels in TCF than intramuscular injection. The penetration after procaine penicillin was very slow. The results showed that the serum peak rather than the area under curve determines the penetration of penicillin. Repeated intramuscular injections of benzylpenicillin and procaine penicillin caused an accumulation of penicillin in TCF. Similar levels were however reached by one single intravenous injection. The clinical counterparts to the used tissue cage model are abscesses. It was concluded that if high penicillin concentration are desireable in such foci, the drug must be given in a way that gives as high serum peaks as possible.
Topics: Animals; Cattle; Extracellular Space; Kinetics; Penicillin G
PubMed: 3565194
DOI: 10.1186/BF03548146 -
Biophysical Journal Oct 2012The effects of substrate binding on class A β-lactamase dynamics were studied using molecular dynamics simulations of two model enzymes; 40 100-ns trajectories of the...
The effects of substrate binding on class A β-lactamase dynamics were studied using molecular dynamics simulations of two model enzymes; 40 100-ns trajectories of the free and substrate-bound forms of TEM-1 (with benzylpenicillin) and PSE-4 (with carbenicillin) were recorded (totaling 4.0 μs). Substrates were parameterized with the CHARMM General Force Field. In both enzymes, the Ω loop exhibits a marked flexibility increase upon substrate binding, supporting the hypothesis of substrate gating. However, specific interactions that are formed or broken in the Ω loop upon binding differ between the two enzymes: dynamics are conserved, but not specific interactions. Substrate binding also has a global structuring effect on TEM-1, but not on PSE-4. Changes in TEM-1's normal modes show long-range effects of substrate binding on enzyme dynamics. Hydrogen bonds observed in the active site are mostly preserved upon substrate binding, and new, transient interactions are also formed. Agreement between NMR relaxation parameters and our theoretical results highlights the dynamic duality of class A β-lactamases: enzymes that are highly structured on the ps-ns timescale, with important flexibility on the μs-ms timescale in regions such as the Ω loop.
Topics: Amino Acid Sequence; Binding Sites; Carbenicillin; Molecular Dynamics Simulation; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Penicillin G; Protein Binding; beta-Lactamases
PubMed: 23083723
DOI: 10.1016/j.bpj.2012.09.009 -
British Heart Journal May 1975A survey of Oxfordshire dentists showed that most practise prophlaxis of bacterial endocarditis, but that few follow currently recommended regimens. for example,...
A survey of Oxfordshire dentists showed that most practise prophlaxis of bacterial endocarditis, but that few follow currently recommended regimens. for example, prophylactic antibiotics are started one or more days before the procedure by 72 per cent of dentists, and two or more days before by 25 per cent. Eight-seven per cent administer antibiotics for a total of four or more days. Penicillin is most often given, but tetracyline remains the commonest second choice. Only 12 per cent use intramuscular drugs as first choice, and procaine penicillin is seldom used. These practices are contrasted with current medical recommendations and discussed with reference to fresh experimental evidence on prevention of bacterial endocarditis.
Topics: Administration, Oral; Anti-Bacterial Agents; Cephalosporins; Clindamycin; Dentistry, Operative; Drug Therapy, Combination; Endocarditis, Bacterial; Erythromycin; Heart Valve Diseases; Humans; Penicillin G; Penicillin V; Penicillins; Surgery, Oral; Surveys and Questionnaires; Tetracycline
PubMed: 805596
DOI: 10.1136/hrt.37.5.478 -
The Journal of Experimental Medicine Jan 19471. In both man and rabbit, penicillin X provided higher and more sustained blood levels than did penicillins F or G similarly administered in equal dosage (0.6 mg. per...
1. In both man and rabbit, penicillin X provided higher and more sustained blood levels than did penicillins F or G similarly administered in equal dosage (0.6 mg. per kg.); while penicillin K gave lower and evanescent levels. (a) One hour after intramuscular injection, the blood levels in rabbits averaged 0.11, 0.18, 0.02, and 0.33 for F, G, K, and X, respectively; and levels of 0.1 mg. per kg. were sustained for 1, 1.4,0.5, and 2.1 hours, respectively. (b) In man, the blood levels of G, K, and X averaged 0.23, 0.16, and 0.37 mg. per kg. 1 hour after intramuscular injections at 0.6 mg. per kg., and 0.11, 0.02, and 0.15 mg. per kg. 1 hour after intravenous injection. (c) In man, a level of 0.1 microgram per cc. was sustained for 1.6, 1.2, and 2.3 hours after the intramuscular injection of G, K, and X, respectively, and for 1, 0.5, and 1.3 hours after their intravenous injection. 2. The total urinary recovery of penicillins F, G, and X varied between 68 and 100 per cent, averaging 61, 87, and 74 per cent, respectively, in rabbits. In man, the urinary recovery of G and X averaged 86 and 93 per cent, respectively. In sharp contrast, the urinary recovery of penicillin K averaged 33 per cent in seven rabbits and 28 per cent in six human volunteers. The major portion of the penicillin appeared in the first 30 to 60 minutes. This suggests a rapid inactivation of penicillin K in vivo. 3. The therapeutic significance of these data is discussed in the text, and in greater detail in the following paper.
Topics: Animals; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Penicillin G; Penicillins; Rabbits
PubMed: 19871605
DOI: 10.1084/jem.85.2.163 -
In vitro activity of cephalothin and three penicillins against Escherichia coli and Proteus species.Antimicrobial Agents and Chemotherapy Sep 1973The susceptibility of clinical isolates of Escherichia coli (67) and Proteus species (58) to cephalothin, ampicillin, benzyl penicillin, and phenoxymethyl penicillin was...
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.
Topics: Ampicillin; Cephalothin; Escherichia coli; Methods; Microbial Sensitivity Tests; Penicillin G; Penicillin Resistance; Penicillin V; Penicillins; Proteus; Proteus mirabilis; Proteus vulgaris
PubMed: 4202343
DOI: 10.1128/AAC.4.3.354 -
The British Journal of Venereal Diseases Dec 1961
Topics: Child; Humans; Inactivation, Metabolic; Penicillin G Benzathine; Penicillins
PubMed: 14484973
DOI: 10.1136/sti.37.4.252 -
Canadian Journal of Veterinary Research... Jul 2001Eight healthy, non-pregnant, crossbred Holstein dairy cows (557-682 kg) within their first 3 months of lactation (13-21.5 kg of milk/day) were used. Cows were kept in...
Penicillin concentrations in serum, milk, and urine following intramuscular and subcutaneous administration of increasing doses of procaine penicillin G in lactating dairy cows.
Eight healthy, non-pregnant, crossbred Holstein dairy cows (557-682 kg) within their first 3 months of lactation (13-21.5 kg of milk/day) were used. Cows were kept in tie stalls for the whole experiment. The 8 cows were randomly assigned to 2 (IM and SC) 4 x 4 balanced Latin square design experiments. Doses of procaine penicillin G (PPG) (300000 IU/mL) in each square were 7000, 14000, 21000 and 28000 IU/kg and were injected IM or SC once daily for 5 consecutive days. Volumes of PPG per site of injection never exceeded 20 mL. Blood was collected to determine the Cmax, Tmax, and AUC; urine and milk were also taken to measure the persistence of PPG in these fluids. Results show that serum Cmax and Tmax were only slightly affected by increasing the doses or the route of administration, whereas the AUC was linearly increased in relation to the dose injected in both modes of injection. In the urine, Cmax varied from 160 to 388 IU/mL and Tmax from 72-120 h during 5 consecutive days of PPG injection. A dose effect in Cmax was observed only for the IM route of administration and no variation (P > 0.05) was found between the IM and SC routes. Milk Cmax concentrations were only increased by the dose regimen in the IM group. At doses of 21000 and 28000 IU/kg, the IM group had a higher (P > 0.05) Cmax when compared with the SC groups. Milk PPG residues were not detectable over 96 h following the last IM injection, independently of the dose injected. However milk PPG residues were detected for up to 132 h following the last SC injection. These results show that when PPG is injected IM once daily in volumes not exceeding 20 mL/site at doses as high as 28000 IU/kg, the withdrawal period should be at least 96 h. Therefore, in the present model, there was no advantage to inject PPG by SC route to improve PPG kinetic parameters as the AUC, Cmax, or Tmax.
Topics: Animals; Area Under Curve; Cattle; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Residues; Female; Injections, Intramuscular; Injections, Subcutaneous; Lactation; Milk; Penicillin G Procaine; Penicillins
PubMed: 11480523
DOI: No ID Found -
The Lancet. Global Health Feb 2017Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality.... (Randomized Controlled Trial)
Randomized Controlled Trial
Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.
BACKGROUND
Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection.
METHODS
We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0-59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429.
FINDINGS
Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and 817 (753 per protocol) were assigned procaine benzylpenicillin, gentamicin, and amoxicillin. Treatment failure within 7 days of enrolment was reported in 90 (12%) infants who received procaine benzylpenicillin and gentamicin (reference), 76 (10%) of those given amoxicillin and gentamicin (risk difference with reference -1·9, 95% CI -5·1 to 1·3), and 99 (13%) of those treated with procaine benzylpenicillin, gentamicin, and amoxicillin (risk difference with reference 1·1, -2·3 to 4·5).
INTERPRETATION
Two simplified antibiotic regimens requiring fewer injections are equivalent to a reference treatment for young infants with signs of clinical severe infection but without signs of critical illness. The use of these simplified regimens has the potential to increase access to treatment for sick young infants who cannot be referred to hospital.
FUNDING
The Saving Newborn Lives initiative of Save the Children, through support from the Bill & Melinda Gates, and by WHO and USAID.
Topics: Ambulatory Care; Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; Female; Gentamicins; Humans; Infant; Infant, Newborn; Male; Pediatrics; Penicillin G Procaine; Referral and Consultation; Sepsis; Severity of Illness Index
PubMed: 27988146
DOI: 10.1016/S2214-109X(16)30335-7