-
Antimicrobial Agents and Chemotherapy May 2018Group B streptococci are common causative agents of early-onset neonatal sepsis (EOS). Pharmacokinetic (PK) data for penicillin G have been described for extremely...
Group 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 () 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 for of 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.).
Topics: Anti-Bacterial Agents; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Microbial Sensitivity Tests; Monte Carlo Method; Penicillin G; Streptococcus
PubMed: 29463540
DOI: 10.1128/AAC.02238-17 -
F1000Research 2023Giant gourami, is the most important freshwater fish species produced by aquaculture in Indonesia. This study aimed to the effects of various newly formulated products...
Effect of feed enriched by products formulated from coconut water, palm sap sugar, and mushroom on the chemical composition of feed and carcass, growth performance, body indices, and gut micromorphology of giant gourami, (Lacepède, 1801), juveniles.
Giant gourami, is the most important freshwater fish species produced by aquaculture in Indonesia. This study aimed to the effects of various newly formulated products on the amino acid composition of the diet and whole-body carcass, and to analyse the growth coefficient, body indices, and gut micromorphology. One hundred gram of palm sap sugar was cooked in 1.1 litre of fresh water for fifteen minutes, to create 1 litre of 11% palm sap sugar solution (after some of it had been boiled off). Two litres of coconut water were then mixed with the litre of palm sugar solution. One litre of this product was added in turn to 2 g of (CP2), 2 g of (CP3), and 2 g of (CP4), while freshwater was used as a control (labeled CP1). Aquafeed was added to CP1, CP2, CP3, and CP4, to make diets labeled KP1, KP2, KP3, and KP4. The dosage was 150 ml/kg of feed. Juvenile giant gourami (initial weight 50±0.25 g and length 13.2±0.07 cm) were reared in triplicate net frames (2×1×1 m; water volume 1.5 m ) in a freshwater concrete pond with a stocking density of 30 juveniles/net. The results supported our hypothesis that different product formulations have a significant effect (P < 0.05) on aquafeed nutrition and the whole-body carcass, growth coefficient, feed utilization, body indices, and gut micromorphology of giant gourami juveniles. The thermal growth coefficient strongly correlated with the daily growth coefficient (r = 92%), condition factor (r = 77%), protein efficiency ratio (r = 75%), while a moderate relationship with the feed intake ( r = 69%). Diet KP3 contains higher total amino acids in diets and carcasses and leads to feed efficiency and better growth for giant gourami.
Topics: Animals; Cocos; Agaricales; Fishes; Diet; Sugars
PubMed: 37822317
DOI: 10.12688/f1000research.124706.2 -
Antimicrobial Agents and Chemotherapy Nov 2015In this study, we aimed to quantify the effects of the N-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolism in vivo and identify other sources of...
In this study, we aimed to quantify the effects of the N-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolism in vivo and identify other sources of pharmacokinetic variability following single-dose administration in healthy Asian adults. The concentrations of INH and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) in plasma were evaluated in 33 healthy Asians who were also given efavirenz and rifampin. The pharmacokinetics of INH, AcINH, and INA were analyzed using nonlinear mixed-effects modeling (NONMEM) to estimate the population pharmacokinetic parameters and evaluate the relationships between the parameters and the elimination status (fast, intermediate, and slow acetylators), demographic status, and measures of renal and hepatic function. A two-compartment model with first-order absorption best described the INH pharmacokinetics. AcINH and INA data were best described by a two- and a one-compartment model, respectively, linked to the INH model. In the final model for INH, the derived metabolic phenotypes for NAT2 were identified as a significant covariate in the INH clearance, reducing its interindividual variability from 86% to 14%. The INH clearance in fast eliminators was 1.9- and 7.7-fold higher than in intermediate and slow eliminators, respectively (65 versus 35 and 8 liters/h). Creatinine clearance was confirmed as a significant covariate for AcINH clearance. Simulations suggested that the current dosing guidelines (200 mg for 30 to 45 kg and 300 mg for >45 kg) may be suboptimal (3 mg/liter ≤ Cmax ≤ 6 mg/liter) irrespective of the acetylator class. The analysis established a model that adequately characterizes INH, AcINH, and INA pharmacokinetics in healthy Asians. Our results refine the NAT2 phenotype-based predictions of the pharmacokinetics for INH.
Topics: Arylamine N-Acetyltransferase; Chromatography, Liquid; Cross-Over Studies; Genotype; Healthy Volunteers; Humans; Isoniazid; Isonicotinic Acids; Polymorphism, Single Nucleotide; Prospective Studies; Tandem Mass Spectrometry
PubMed: 26282412
DOI: 10.1128/AAC.01244-15 -
Antimicrobial Agents and Chemotherapy Oct 2019Evaluation of dosing regimens for critically ill patients requires pharmacokinetic data in this population. This prospective observational study aimed to describe the...
Evaluation of dosing regimens for critically ill patients requires pharmacokinetic data in this population. This prospective observational study aimed to describe the population pharmacokinetics of unbound ceftolozane and tazobactam in critically ill patients without renal impairment and to assess the adequacy of recommended dosing regimens for treatment of systemic infections. Patients received 1.5 or 3.0 g ceftolozane-tazobactam according to clinician recommendation. Unbound ceftolozane and tazobactam plasma concentrations were assayed, and data were analyzed with Pmetrics with subsequent Monte Carlo simulations. A two-compartment model adequately described the data from twelve patients. Urinary creatinine clearance (CL) and body weight described between-patient variability in clearance and central volume of distribution (), respectively. Mean ± standard deviation (SD) parameter estimates for unbound ceftolozane and tazobactam, respectively, were CL of 7.2 ± 3.2 and 25.4 ± 9.4 liters/h, of 20.4 ± 3.7 and 32.4 ± 10 liters, rate constant for distribution of unbound ceftolozane or tazobactam from central to peripheral compartment (Kcp) of 0.46 ± 0.74 and 2.96 ± 8.6 h, and rate constant for distribution of unbound ceftolozane or tazobactam from peripheral to central compartment (Kpc) of 0.39 ± 0.37 and 26.5 ± 8.4 h With dosing at 1.5 g and 3.0 g every 8 h (q8h), the fractional target attainment (FTA) against was ≥85% for directed therapy (MIC ≤ 4 mg/liter). However, for empirical coverage (MIC up to 64 mg/liter), the FTA was 84% with the 1.5-g q8h regimen when creatinine clearance is 180 ml/min/1.73 m, whereas the 3.0-g q8h regimen consistently achieved an FTA of ≥85%. For a target of 40% of time the free drug concentration is above the MIC (40% T), 3g q8h by intermittent infusion is suggested unless a highly susceptible pathogen is present, in which case 1.5-g dosing could be used. If a higher target of 100% T is required, a 1.5-g loading dose plus a 4.5-g continuous infusion may be adequate.
Topics: Anti-Bacterial Agents; Cephalosporins; Critical Illness; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Pseudomonas aeruginosa; Tazobactam
PubMed: 31358583
DOI: 10.1128/AAC.01265-19 -
Kidney International Jan 1983Intra-abdominal pressure (IAP), forced vital capacity (FVC), and forced expiratory volume at 1 sec (FEV1) were measured in 18 stable continuous ambulatory peritoneal... (Comparative Study)
Comparative Study
Intra-abdominal pressure (IAP), forced vital capacity (FVC), and forced expiratory volume at 1 sec (FEV1) were measured in 18 stable continuous ambulatory peritoneal dialysis (CAPD) patients maintained on 2-liter exchanges, in the supine, sitting, and upright positions after infusing dialysis solutions in 0.5-liter increments up to 4 liters as tolerated. Thereafter, five patients did not increase to 3-liter volumes (RUT-0), four used 3-liter volumes occasionally (RUT-1), and nine chose 3-liter volumes for routine dialysis (RUT-2). IAP was similar in all groups and dependent on the intraperitoneal volume (IPV). The mean IAP increased 2.0, 2.7, and 2.8 cm H2O/liter of IPV in the supine, upright, and sitting positions, respectively. The patients of the RUT-0 group had dramatic deterioration (up to 42%) of FVC and FEV1 in the supine position with IPV above 2 liters. The patients with the greatest deterioration of pulmonary functions could not continue the measurements above 3 liters of IPV. Two of these patients were switched to 1-liter overnight exchanges. Even in patients who tolerated up to 4 liters, FVC and FEV1 decreased significantly in the supine and sitting positions, with IPV greater than 3 or 4 liters, respectively. In the upright position, the values did not decrease significantly below those with the empty abdomen up to 4.6 liters of IPV. Each liter of IPV increased the abdominal girth by 2.1 cm. Exchange volume and frequency should be individualized. In our studies, 50% of the patients could increase daily dialysate volume from 8 to 9 liters while decreasing daily exchanges from 4 to 3.
Topics: Abdomen; Adult; Aged; Analysis of Variance; Female; Forced Expiratory Volume; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Posture; Pressure; Solutions; Time Factors; Vital Capacity
PubMed: 6834695
DOI: 10.1038/ki.1983.12 -
Antimicrobial Agents and Chemotherapy Jun 2018To date, there is no information on the intravenous (i.v.) posaconazole pharmacokinetics for intensive care unit (ICU) patients. This prospective observational study... (Clinical Trial)
Clinical Trial
To date, there is no information on the intravenous (i.v.) posaconazole pharmacokinetics for intensive care unit (ICU) patients. This prospective observational study aimed to describe the pharmacokinetics of a single dose of i.v. posaconazole in critically ill patients. Patients with no history of allergy to triazole antifungals and requiring systemic antifungal therapy were enrolled if they were aged ≥18 years, central venous access was available, they were not pregnant, and they had not received prior posaconazole or drugs interacting with posaconazole. A single dose of 300 mg posaconazole was administered over 90 min. Total plasma concentrations were measured from serial plasma samples collected over 48 h, using a validated chromatographic method. The pharmacokinetic data set was analyzed by noncompartmental methods. Eight patients (7 male) were enrolled with the following characteristics: median age, 46 years (interquartile range [IQR], 40 to 51 years); median weight, 68 kg (IQR, 65 to 82 kg); and median albumin concentration, 20 g/liter (IQR, 18 to 24 g/liter). Median (IQR) pharmacokinetic parameter estimates were as follows: observed maximum concentration during sampling period (), 1,702 ng/ml (1,352 to 2,141 ng/ml); area under the concentration-time curve from zero to infinity (AUC), 17,932 ng · h/ml (13,823 to 27,905 ng · h/ml); clearance (CL), 16.8 liters/h (11.1 to 21.7 liters/h); and volume of distribution (), 529.1 liters (352.2 to 720.6 liters). The and CL were greater than 2-fold and the AUC was 39% of the values reported for heathy volunteers. The AUC was only 52% of the steady-state AUC reported for hematology patients. The median of estimated average steady-state concentrations was 747 ng/ml (IQR, 576 to 1,163 ng/ml), which is within but close to the lower end of the previously recommended therapeutic range of 500 to 2,500 ng/ml. In conclusion, we observed different pharmacokinetics of i.v. posaconazole in this cohort of critically ill patients compared to those in healthy volunteers and hematology patients.
Topics: Administration, Intravenous; Adult; Antifungal Agents; Critical Illness; Female; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Triazoles
PubMed: 29581122
DOI: 10.1128/AAC.00242-18 -
Annals of Cardiac Anaesthesia 2022Fluid resuscitation during Off-Pump Coronary Surgery (OPCABG) is still not protocolized and depends on multiple variables. We are exploring in this study whether a...
BACKGROUND
Fluid resuscitation during Off-Pump Coronary Surgery (OPCABG) is still not protocolized and depends on multiple variables. We are exploring in this study whether a restrictive or euvolemic approach has any impact on short term surgical outcomes following OPCABG.
METHODS
It is a retrospective study of 300 patients analyzed based on the intraoperative fluid requirement with 150 patients in each group (Group I: Fluid <2 Litres, Group II: Fluid >2 Litres).
RESULTS
Multivariable analysis showed echocardiography variables such as E/e ratio, LA volume index, and atrial fibrillation (AF). LA volume index is related to the higher fluid requirement. Group II had significantly higher ventilation time (P < 0.05), drain output (P = 0.05), drain removal time (<0.05), inotropic requirement, and diuretic use.
CONCLUSION
The requirement of the intraoperative fluid was associated with various factors including diastolic dysfunction (left atrial volume index, left ventricle mass index, E/e ratio) and preoperative dual antiplatelet use. Group II patients had longer ventilation time, diuretics use, high drain output, and required drains for a longer period of time. Although there was no statistical difference among two groups as far as postoperative AF concerned, a reversal of AF to sinus rhythm was delayed in group II patients.
Topics: Atrial Fibrillation; Coronary Artery Bypass; Echocardiography; Heart Atria; Humans; Retrospective Studies
PubMed: 35075015
DOI: 10.4103/aca.ACA_139_20 -
Danish Medical Bulletin Jul 2010The purpose of this thesis was to describe pathophysiological aspects of perioperative fluid administration and create a rational background for future, clinical outcome... (Review)
Review
The purpose of this thesis was to describe pathophysiological aspects of perioperative fluid administration and create a rational background for future, clinical outcome studies. In laparoscopic cholecystectomy, we have found "liberal" crystalloid administration ( approximately 3 liters) to improve perioperative physiology and clinical outcome, which has implication for fluid management in other laparoscopic procedures such as laparoscopic fundoplication, laparoscopic repair of ventral hernia, hysterectomy etc., where 2-3 liters crystalloid should be administered based on the present evidence. That equal amounts of fluid caused adverse physiologic effects in healthy volunteers indicates that addition of the surgical trauma per se increases fluid requirements. Volume kinetic analysis applied 4 hours postoperatively was not able to detect the presence of either overhydration or hypovolemia regardless of the administered fluid volume intraoperatively. In knee arthroplasty a approximately 4 vs. approximately 2 liters crystalloid-based fluid regimen lead to significant hypercoagulability (although with unknown clinical implications), but no over-all differences in functional recovery. Dehydration caused by bowel preparation leads to functional hypovolemia and the deficits should be corrected, in particular in elderly patients, where preoperative intravenous fluid substitution of approximately 2-3 liters crystalloid is recommended. We did not find thoracic epidural anesthesia to be accompanied by intravascular fluid mobilization. In major (colonic) surgery with a standardized multimodal rehabilitation regimen, over-all functional recovery was not affected with a "liberal" ( approximately 5 liters) vs. "restrictive" 1.5 liter crystalloid-based regimen, however based on three anastomotic leakages in the "restrictive" group, it may be hypothesized that a too "restrictive" fluid administration strategy could be detrimental in patients with anastomoses and need further evaluation. A systematic review concluded that present evidence does not allow final recommendations on which type of fluid to administer in elective surgery. Based on the current evidence, administration of < 5 liters intravenous fluid without specific indication in major surgical procedures should be avoided, while administration of < 1.5 liters in patients with anastomoses may not be recommended, an issue needing clarification in large-scale clinical studies. Finally, we have demonstrated that the conduction of double-blinded randomized trials on fluid management with postoperative outcomes is feasible.
Topics: Elective Surgical Procedures; Fluid Therapy; Humans; Hypovolemia; Length of Stay; Perioperative Care; Postoperative Complications; Renal Dialysis; Risk Factors; Time Factors; Wound Healing
PubMed: 20591343
DOI: No ID Found -
Veterinary Medicine International 2020There is a growing interest in protein supplementation of dairy-cow diets using leguminous shrubs. The study objective was to ascertain the association between diet...
There is a growing interest in protein supplementation of dairy-cow diets using leguminous shrubs. The study objective was to ascertain the association between diet supplementation with and and milk production in dairy cattle on commercial smallholder farms. This trial involved 235 cows from 80 smallholder dairy farms in Kenya randomly allocated to 4 intervention groups: (1) receiving and and nutritional advice; (2) receiving reproductive medicines and advice; (3) receiving both group 1 and 2 interventions; and (4) receiving neither intervention. Farm nutritional practices and management data were collected in a questionnaire, and subsequent physical examinations, mastitis tests, and milk production of cows on the farm were monitored approximately monthly for 16 months. Descriptive and univariable statistical analyses were conducted, and multivariable mixed-model regression was used for identification of factors associated ( < 0.05) with daily milk production. The mean milk production was 6.39 liters/cow/day (SD = 3.5). Feeding to cows was associated ( < 0.0005) with an increase in milk produced by at least 1 liter/cow/day with each kg fed. Other variables positively associated with ln daily milk production in the final model included feeding of Napier grass, amount of silage and dairy meal fed, body condition score, and appetite of the cow. Other variables negatively associated with ln daily milk production in the final model included amount of maize germ fed, days in milk, sudden feed changes, pregnancy, and subclinical mastitis. In conclusion, our field trial data suggest that use of / through agroforestry can improve milk production in commercial smallholder dairy farms in Kenya. Agroforestry land use systems can be adopted as a way for dairy farmers to cope with feed shortages and low crude protein in farm-available feeds for their cows.
PubMed: 32148747
DOI: 10.1155/2020/3262370 -
Journal of the American Mosquito... Jun 2016Gravid mosquito collections were compared among several large-volume (infusion volume ≥35 liters) gravid trap designs and the small-volume (infusion volume = 6... (Comparative Study)
Comparative Study
Gravid mosquito collections were compared among several large-volume (infusion volume ≥35 liters) gravid trap designs and the small-volume (infusion volume = 6 liters) Centers for Disease Control and Prevention (CDC) gravid trap used routinely by vector control districts for vector and pathogen surveillance. The numbers of gravid Culex quinquefasciatus, Cx. tarsalis, and Cx. stigmatosoma collected by large gravid traps were greater than by the CDC gravid trap during nearly all overnight trials. Large-volume gravid traps collected on average 6.6-fold more adult female Culex mosquitoes compared to small-volume CDC gravid traps across 3 seasons during the 3 years of the studies. The differences in gravid mosquito collections between large-versus small-volume gravid traps were greatest during spring, when 8- to 56-fold more Culex individuals were collected using large-volume gravid traps. The proportion of gravid females in collections did not differ appreciably among the more effective trap designs tested. Important determinants of gravid trap performance were infusion container size and type as well as infusion volume, which determined the distance between the suction trap and the infusion surface. Of lesser importance for gravid trap performance were the number of suction traps, method of suction trap mounting, and infusion concentration. Fermentation of infusions between 1 and 4 wk weakly affected total mosquito collections, with Cx. stigmatosoma collections moderately enhanced by comparatively young and organically enriched infusions. A suction trap mounted above 100 liters of organic infusion housed in a 121-liter black plastic container collected the most gravid mosquitoes over the greatest range of experimental conditions, and a 35-liter infusion with side-mounted suction traps was a promising lesser-volume alternative design.
Topics: Animals; California; Culex; Female; Insect Vectors; Male; Mosquito Control
PubMed: 27280347
DOI: 10.2987/moco-32-02-91-102.1