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Antimicrobial Agents and Chemotherapy Feb 1990A regimen of a single intramuscular dose of penicillin G-streptomycin was compared with regimens of three oral doses of amoxicillin and two oral doses of penicillin V to...
Tolerance and efficacy of parenterally administered penicillin-streptomycin and orally administered amoxicillin or penicillin V for prophylaxis of experimentally induced streptococcal endocarditis.
A regimen of a single intramuscular dose of penicillin G-streptomycin was compared with regimens of three oral doses of amoxicillin and two oral doses of penicillin V to prevent Streptococcus sanguis endocarditis in rabbits with experimentally induced valvular heart lesions. Challenge doses of 10(4), 10(6), and 10(8) CFU of a strain of S. sanguis highly tolerant to penicillin and amoxicillin were used. The combination of penicillin and streptomycin was the only regimen tested that provided full protection even against the highest inoculum concentration. A single oral dose of penicillin V (36 mg/kg) or amoxicillin (50 mg/kg), two oral doses of penicillin V (36 and 18 mg/kg with a 7-h interval between doses), or six oral doses of amoxicillin (50 mg/kg followed by 8.5 mg/kg at 8-h intervals) protected recipients of the lowest inoculum concentration; protection diminished with increasing inocula. In contrast, administration of two high oral doses of amoxicillin (50 mg/kg) with a 10-h interval between doses provided full protection against challenge doses of 10(4) and 10(6) CFU, preventing endocarditis in 10 (66%) of 15 recipients of 10(8) CFU. All regimens evaluated were highly effective in preventing endocarditis when rabbits were challenged with 10(4) CFU. The combination of penicillin and streptomycin was the best regimen tested. Administration of two high oral doses of amoxicillin (50 mg/kg) with a 10-h interval between doses led to significantly fewer infections when compared with the other oral regimens when rabbits were challenged with 10(6) and 10(8) CFU.
Topics: Amoxicillin; Animals; Drug Therapy, Combination; Endocarditis, Bacterial; Microbial Sensitivity Tests; Penicillin G; Penicillin V; Penicillins; Rabbits; Streptococcal Infections; Streptococcus sanguis; Streptomycin
PubMed: 2109579
DOI: 10.1128/AAC.34.2.321 -
British Medical Journal Oct 1964
Topics: Drug Therapy; Methicillin; Penicillin G; Penicillin Resistance; Penicillins; Staphylococcal Infections; Statistics as Topic
PubMed: 14185666
DOI: 10.1136/bmj.2.5414.940 -
The Journal of Antimicrobial... Sep 2023Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care.
The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA): investigating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin pharmacokinetics from birth to adolescence.
BACKGROUND
Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care.
OBJECTIVES
The primary objective of the Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA) was to characterize PK profiles of commonly used penicillins using data obtained during routine care, to further understanding of PK variability and inform future evidence-based dosing.
METHODS
NAPPA was a multicentre study of amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin/tazobactam. Patients were recruited with informed consent. Antibiotic dosing followed standard of care. PK samples were obtained opportunistically or at optimal times, frozen and analysed using UPLC with tandem MS. Pharmacometric analysis was undertaken using NONMEM software (v7.3). Model-based simulations (n = 10 000) tested PTA with British National Formulary for Children (BNFC) and WHO dosing. The study had ethical approval.
RESULTS
For the combined IV PK model, 963 PK samples from 370 participants were analysed simultaneously incorporating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin data. BNFC high-dose regimen simulations gave these PTA results (median fT>MIC at breakpoints of specified pathogens): amoxicillin 100% (Streptococcus pneumoniae); benzylpenicillin 100% (Group B Streptococcus); flucloxacillin 48% (MSSA); and piperacillin 100% (Pseudomonas aeruginosa). Oral population PK models for flucloxacillin and amoxicillin enabled estimation of first-order absorption rate constants (1.16 h-1 and 1.3 h-1) and bioavailability terms (62.7% and 58.7%, respectively).
CONCLUSIONS
NAPPA represents, to our knowledge, the largest prospective combined paediatric penicillin PK study undertaken to date, and the first paediatric flucloxacillin oral PK model. The PTA results provide evidence supportive of BNFC high-dose IV regimens for amoxicillin, benzylpenicillin and piperacillin.
Topics: Infant, Newborn; Humans; Child; Adolescent; Piperacillin; Floxacillin; Amoxicillin; Prospective Studies; Anti-Bacterial Agents; Penicillins; Microbial Sensitivity Tests
PubMed: 37531085
DOI: 10.1093/jac/dkad196 -
The Cochrane Database of Systematic... Feb 2019Congenital syphilis continues to be a substantial public health problem in many parts of the world. Since the first use of penicillin for the treatment of syphilis in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital syphilis continues to be a substantial public health problem in many parts of the world. Since the first use of penicillin for the treatment of syphilis in 1943, which was a notable early success, it has remained the preferred and standard treatment including for congenital syphilis. However, the treatment of congenital syphilis is largely based on clinical experience and there is extremely limited evidence on the optimal dose or duration of administration of penicillin or the use of other antibiotics.
OBJECTIVES
To assess the effectiveness and safety of antibiotic treatment for newborns with confirmed, highly probable and possible congenital syphilis.
SEARCH METHODS
We searched the Cochrane STI Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, WHO ICTRP, ClinicalTrials.gov and Web of Science to 23 May 2018. We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing antibiotic treatment (any concentration, frequency, duration and route) with no intervention or any other antibiotic treatment for neonates with confirmed, highly probable or possible congenital syphilis.
DATA COLLECTION AND ANALYSIS
All review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
Two RCTs (191 participants) met our inclusion criteria and none of these trials was funded by the industry. One trial (22 participants) compared benzathine penicillin with no intervention for infants with possible congenital syphilis. Low-quality evidence suggested that benzathine penicillin administration may not have decreased the rate of neonatal death due to any cause (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.06 to 11.70), and showed a possible reduction into the proportion of neonates with clinical manifestations of congenital syphilis (RR 0.12, 95% CI 0.01 to 2.09). Penicillin administration increased the serological cure at the third month (RR 2.13, 95% CI 1.06 to 4.27). These results should be taken with caution, because the trial was stopped early because there were four cases with clinical congenital syphilis in the no treatment group and none in the treatment group. Interim analysis suggested this difference was significant. This study did not report neonatal death due to congenital syphilis or the frequency of serious or minor adverse events after therapy. We downgraded the quality of evidence because of imprecision and risk of bias.One trial (169 participants) compared benzathine penicillin versus procaine benzylpenicillin. High- and moderate-quality evidence suggested that there were probably no differences between benzathine penicillin and procaine benzylpenicillin for the outcomes: absence of clinical manifestations of congenital syphilis (RR 1.00, 95% CI 0.97 to 1.03) and serological cure (RR 1.00, 95% CI 0.97 to 1.03). There were no cases of neonatal death due congenital syphilis; all 152 babies who followed up survived. This study did not report on the frequency of serious or minor adverse events after therapy. We downgraded the quality of evidence because of serious risk of bias.
AUTHORS' CONCLUSIONS
At present, the evidence on the effectiveness and safety of antibiotic treatment for newborns with confirmed, highly probable or possible congenital syphilis is sparse, implying that we are uncertain about the estimated effect. One trial compared benzathine penicillin with no intervention for infants with possible congenital syphilis. Low-quality evidence suggested penicillin administration possibly reduce the proportion of neonates with clinical manifestations of congenital syphilis, penicillin administration increased the serological cure at the third month. These findings support the clinical use of penicillin in neonates with confirmed, highly probable or possible congenital syphilis. High- and moderate-quality evidence suggests that there are probably no differences between benzathine penicillin and procaine benzylpenicillin administration for the outcomes of absence of clinical manifestations of syphilis or serological cure.
Topics: Anti-Bacterial Agents; Humans; Infant; Infant Mortality; Infant, Newborn; Penicillin G Benzathine; Penicillin G Procaine; Randomized Controlled Trials as Topic; Syphilis, Congenital
PubMed: 30776081
DOI: 10.1002/14651858.CD012071.pub2 -
British Journal of Pharmacology and... Aug 1961The pharmacology of a new antibiotic methicillin, 6(2:6-dimethoxybenzamido)-penicillanic acid, which is effective against staphylococci resistant to penicillin G, has...
The pharmacology of a new antibiotic methicillin, 6(2:6-dimethoxybenzamido)-penicillanic acid, which is effective against staphylococci resistant to penicillin G, has been investigated. It is free from acute and chronic toxic effects, except that some pain may be caused following intramuscular injection. It is poorly absorbed orally, but after intramuscular injection the concentrations in the serum and in tissues are very similar to those found with penicillin G. It is excreted by the kidneys both by renal tubular secretion and glomerular filtration. It is also excreted in the bile in very high concentrations, the ratio of concentration in the bile to the blood being approximately 2.5 times that of penicillin G. From a study of the metabolism of the drug it is calculated that 75% is eliminated unchanged in the urine and that the remainder is probably destroyed after the excretion into the intestine via the bile.
Topics: Bile; Biological Transport; Body Fluids; Humans; Injections, Intramuscular; Kidney; Methicillin; Pain; Penicillanic Acid; Penicillin G; Penicillins; Staphylococcus
PubMed: 13681272
DOI: 10.1111/j.1476-5381.1961.tb01105.x -
British Medical Journal Oct 1978
Topics: Adult; Brain Diseases; Child; Drug Administration Schedule; Humans; Infant; Injections, Spinal; Penicillin G
PubMed: 581353
DOI: 10.1136/bmj.2.6144.1090-a -
The Western Journal of Medicine Oct 1988
Topics: Adolescent; Agranulocytosis; Endocarditis, Bacterial; Female; Humans; Penicillin G; Streptococcal Infections; Streptococcus
PubMed: 3227691
DOI: No ID Found -
The British Journal of Ophthalmology Jan 1997
Topics: Adult; Anterior Chamber; Eye Infections, Bacterial; Fluorescein Angiography; Humans; Male; Pain; Penicillin G Benzathine; Penicillins; Treponemal Infections
PubMed: 9135419
DOI: 10.1136/bjo.81.1.90b -
British Medical Journal Apr 1971
Topics: Adult; Cloxacillin; Female; Humans; Meningitis; Penicillin G; Spinal Puncture; Streptococcal Infections
PubMed: 5581498
DOI: 10.1136/bmj.2.5754.166-b -
International Journal of Molecular... Jun 2022Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs)....
Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillins.
Topics: Amoxicillin; Drug Hypersensitivity; Humans; Hypersensitivity, Immediate; Immunoenzyme Techniques; Immunoglobulin E; Penicillin G; Penicillins; Skin Tests
PubMed: 35805992
DOI: 10.3390/ijms23136992