scholarly journals Pharmacokinetics of Penicillin G in Preterm and Term Neonates

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Helgi Padari ◽  
Tuuli Metsvaht ◽  
Eva Germovsek ◽  
Charlotte I. Barker ◽  
Karin Kipper ◽  
...  
Keyword(s):  
Compartment Model ◽  
Interquartile Range ◽  
Penicillin G ◽  
Preterm Neonates ◽  
Parameter Estimates ◽  
Group B Streptococci ◽  
Term Neonates ◽  
Extremely Preterm ◽  
Population Pk ◽  
Group B

ABSTRACTGroup B streptococci are common causative agents of early-onset neonatal sepsis (EOS). Pharmacokinetic (PK) data for penicillin G have been described for extremely preterm neonates but have been poorly described for late-preterm and term neonates. Thus, evidence-based dosing recommendations are lacking. We describe the PK of penicillin G in neonates with a gestational age (GA) of ≥32 weeks and a postnatal age of <72 h. Penicillin G was administered intravenously at a dose of 25,000 or 50,000 IU/kg of body weight every 12 h (q12h). At steady state, PK blood samples were collected prior to and at 5 min, 1 h, 3 h, 8 h, and 12 h after injection. Noncompartmental PK analysis was performed with WinNonlin software. With those data in combination with data from neonates with a GA of ≤28 weeks, we developed a population PK model using NONMEM software and performed probability of target attainment (PTA) simulations. In total, 16 neonates with a GA of ≥32 weeks were included in noncompartmental analysis. The median volume of distribution (V) was 0.50 liters/kg (interquartile range, 0.42 to 0.57 liters/kg), the median clearance (CL) was 0.21 liters/h (interquartile range, 0.16 to 0.29 liters/kg), and the median half-life was 3.6 h (interquartile range, 3.2 to 4.3 h). In the population PK analysis that included 35 neonates, a two-compartment model best described the data. The final parameter estimates were 10.3 liters/70 kg and 29.8 liters/70 kg forVof the central and peripheral compartments, respectively, and 13.2 liters/h/70 kg for CL. Considering the fraction of unbound penicillin G to be 40%, the PTA of an unbound drug concentration that exceeds the MIC for 40% of the dosing interval was >90% for MICs of ≤2 mg/liter with doses of 25,000 IU/kg q12h. In neonates, regardless of GA, the PK parameters of penicillin G were similar. The dose of 25,000 IU/kg q12h is suggested for treatment of group B streptococcal EOS diagnosed within the first 72 h of life. (This study was registered with the EU Clinical Trials Register under EudraCT number 2012-002836-97.)

scholarly journals Changes in incidence and etiology of early-onset neonatal infections 1997–2017 – a retrospective cohort study in western Sweden

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Margrét Johansson Gudjónsdóttir ◽  
Anders Elfvin ◽  
Elisabet Hentz ◽  
Ingegerd Adlerberth ◽  
Ingemar Tessin ◽  
...  
Keyword(s):  
Early Onset ◽  
Antimicrobial Prophylaxis ◽  
List Type ◽  
Neonatal Infections ◽  
Group B Streptococci ◽  
Gram Negative ◽  
Live Births ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Group B

Abstract Background The objective of the study was to evaluate data on early-onset neonatal invasive infections in western Sweden for the period 1997–2017. To identify changes in incidence, etiology and mortality and compare to previous studies from the same area starting from 1975. Methods Observational epidemiological, retrospective study on infants 0–6 days of age with a positive culture in blood and/or cerebrospinal fluid between 1997 and 2017. A comparison was made of the incidence between 2008 and 2017 compared to 1997–2007. Changes in the incidence of infections due to Group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods were assessed from 1975. Results The total incidence, including both recognized pathogens and commensals as causative agents, was 1.1/1000 live births. The incidence declined from 1.4/1000 LB in 1997–2007 to 0.9/1000 LB in 2008–2017 but the case-fatality rate remained unchanged, (8/119 vs 7/90), at 7%. Among the 209 patients identified during 1997–2017 with sepsis or meningitis the most common organisms were Group B streptococci (40%, 84/209), S. aureus (16%, 33/209) and E. coli (9%, 18/209). The incidence of Group B streptococci infections went from 0.9/1000 live births 1987–1996 to 0.45/1000 live births 1997–2017 and all cases were within 72 h. The proportion of extremely preterm infants (< 28 weeks gestation) rose steadily during the study period but there was no rise in infections due to Gram-negative organisms. The spectrum of cultured organisms changed after 72 h as commensal organisms started to emerge. Conclusion There has been a decrease in the incidence of neonatal early-onset infections compared to previous studies in western Sweden. The incidence of GBS infections was not as low as in other reports. Further studies are needed to assess if screening-based intra partum antimicrobial prophylaxis instead of a risk factor-based approach for identifying candidates for intrapartum antimicrobial prophylaxis would be a better option for this study area. Key notes This study is one of the longest running follow-ups in the world, a follow-up of 43 years of early-onset neonatal infections.The incidence of early-onset GBS infections is higher in Western Sweden compared to other local reports.No difference in the incidence of early-onset GBS depending on the definition of early-onset being within 72 h or 7 days of life.

scholarly journals Impaired phagocytosis and opsonisation towards group B streptococci in preterm neonates

1998 ◽  
Vol 78 (1) ◽  
pp. F46-F50 ◽  
Author(s):  
J. Kallman ◽  
J. Schollin ◽  
C. Schalen ◽  
A. Erlandsson ◽  
E. Kihlstrom
Keyword(s):  
Preterm Neonates ◽  
Group B Streptococci ◽  
Group B

scholarly journals Effect of gestational age and postnatal age on the endothelial glycocalyx in neonates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexandra Puchwein-Schwepcke ◽  
Stefanie Artmann ◽  
Lea Rajwich ◽  
Orsolya Genzel-Boroviczény ◽  
Claudia Nussbaum
Keyword(s):  
Gestational Age ◽  
Boundary Region ◽  
Vascular Pathology ◽  
Endothelial Glycocalyx ◽  
Preterm Neonates ◽  
Extrinsic Factors ◽  
Term Neonates ◽  
Group A ◽  
Underlying Mechanisms ◽  
Group B

AbstractPrematurity predisposes to cardiovascular disease; however the underlying mechanisms remain elusive. Disturbance of the endothelial glycocalyx (EG), an important regulator of vessel function, is thought to contribute to vascular pathology. Here, we studied the EG with respect to gestational and postnatal age in preterm and term neonates. The Perfused Boundary Region (PBR), an inverse measure of glycocalyx thickness, was measured postnatally in 85 term and 39 preterm neonates. Preterm neonates were further analyzed in two subgroups i.e., neonates born < 30 weeks gestational age (group A) and neonates born ≥ 30 weeks (group B). In preterm neonates, weekly follow-up measurements were performed if possible. PBR differed significantly between preterm and term neonates with lowest values representing largest EG dimension in extremely premature infants possibly reflecting its importance in fetal vascular development. Linear regression revealed a dependence of PBR on both, gestational age and postnatal age. Furthermore, hematocrit predicted longitudinal PBR changes. PBR measured in group A at a corrected age of > 30 weeks was significantly higher than in group B at birth, pointing towards an alteration of intrinsic maturational effects by extrinsic factors. These changes might contribute to the increased cardiovascular risk associated with extreme prematurity.

scholarly journals Antimicrobial Susceptibilities of Group B Streptococci Isolated between 1992 and 1996 from Patients with Bacteremia or Meningitis

1998 ◽  
Vol 42 (6) ◽  
pp. 1517-1519 ◽  
Author(s):  
Marisol Fernandez ◽  
Melissa E. Hickman ◽  
Carol J. Baker
Keyword(s):  
Penicillin G ◽  
Group B Streptococci ◽  
Streptococcal Disease ◽  
Drug Of Choice ◽  
Treatment And Prevention ◽  
Invasive Infections ◽  
Group B Streptococcal Disease ◽  
Continued Use ◽  
Group B

ABSTRACT In vitro testing of 229 group B streptococcal isolates from a variety of patients with invasive infections indicated uniform penicillin G susceptibility. However, 17 (7.4%) isolates were resistant to erythromycin and 8 (3.4%) were resistant to clindamycin. These results support the continued use of penicillin G as the drug of choice for the treatment and prevention of group B streptococcal disease.

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

2014 ◽  
Vol 58 (8) ◽  
pp. 4495-4503 ◽  
Author(s):  
Mengjie Li ◽  
Ronette Gehring ◽  
Lisa Tell ◽  
Ronald Baynes ◽  
Qingbiao Huang ◽  
...  
Keyword(s):  
Compartment Model ◽  
Penicillin G ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Pharmacokinetic Studies ◽  
Population Parameter ◽  
Concentration Data ◽  
Mixed Effect ◽  
Animal Products ◽  
Swine Liver

ABSTRACTExtralabel 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.

scholarly journals Population Pharmacokinetics Analysis of Amikacin Initial Dosing Regimen in Elderly Patients

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 100
Author(s):  
Hideo Kato ◽  
Suzanne L. Parker ◽  
Jason A. Roberts ◽  
Mao Hagihara ◽  
Nobuhiro Asai ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Compartment Model ◽  
The Elderly ◽  
Volume Of Distribution ◽  
Parameter Estimates ◽  
Limited Data ◽  
Dosing Regimen ◽  
Population Pk ◽  
Dosing Regimens ◽  
Dosing Intervals

There are limited data of amikacin pharmacokinetics (PK) in the elderly population. Hence, we aimed to describe the population PK of amikacin in elderly patients (>70 years old) and to establish optimized initial dosing regimens. We simulated individual maximum concentrations in plasma (Cmax) and minimal concentrations (Cmin) for several dosing regimens (200–2000 mg every 24, 48, and 72 h) for patients with creatinine clearance (CCr) of 10–90 mL/min and analyzed efficacy (Cmax/minimal inhibitory concentration (MIC) ≥ 8) for MICs of 4, 8, and 16 mg/L and safety (Cmin < 4 mg/L). A one-compartment model best described the data. CCr was the only covariate associated with amikacin clearance. The population PK parameter estimates were 2.25 L/h for clearance and 18.0 L for volume of distribution. Dosing simulations recommended the dosing regimens (1800 mg) with dosing intervals ranging 48–72 h for patients with CCr of 40–90 mL/min based on achievement of both efficacy for the MIC of 8 mg/L and safety. None of the dosing regimens achieved the targets for an MIC of 16 mg/L. We recommend the initial dosing regimen using a nomogram based on CCr for an MIC of ≤8 mg/L in elderly patients with CCr of 40–90 mL/min.

scholarly journals Effect of Obesity on the Population Pharmacokinetics of Meropenem in Critically Ill Patients

2016 ◽  
Vol 60 (8) ◽  
pp. 4577-4584 ◽  
Author(s):  
Abdulaziz S. Alobaid ◽  
Steven C. Wallis ◽  
Paul Jarrett ◽  
Therese Starr ◽  
Janine Stuart ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Compartment Model ◽  
Central Compartment ◽  
Lower Probability ◽  
Peripheral Compartment ◽  
Morbidly Obese ◽  
Parameter Estimates ◽  
Population Pk ◽  
Intercompartmental Clearance

ABSTRACTSevere pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index (BMI) groups: nonobese (18.5 to 29.9 kg/m2), obese (30.0 to 39.9 kg/m2), and morbidly obese (≥40 kg/m2). Serial plasma samples were taken, and meropenem concentrations were determined using a validated chromatographic method. Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Nineteen critically ill patients with different BMI categories were enrolled. The patients' mean ± standard deviation (SD) age, weight, and BMI were 49 ± 15.9 years, 95 ± 22.0 kg, and 33 ± 7.0 kg/m2, respectively. A two-compartment model described the data adequately. The mean ± SD parameter estimates for the final covariate model were as follows: clearance (CL), 15.5 ± 6.0 liters/h; volume of distribution in the central compartment (V1), 11.7 ± 5.8 liters; intercompartmental clearance from the central compartment to the peripheral compartment, 25.6 ± 35.1 liters h−1; and intercompartmental clearance from the peripheral compartment to the central compartment, 8.32 ± 12.24 liters h−1. Higher creatinine clearance (CLCR) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increasedV1, dose adjustment based on CLCRappears to be more important than patient BMI.

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