scholarly journals Simplified Dosing Regimens for Gentamicin in Neonatal Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
S. D’Agate ◽  
F. Tshinanu Musuamba ◽  
E. Jacqz-Aigrain ◽  
O. Della Pasqua
Keyword(s):  
Body Weight ◽  
Bacterial Infections ◽  
Drug Disposition ◽  
External Validation ◽  
World Health ◽  
Fixed Dose ◽  
Therapeutic Drug ◽  
Resource Limited Settings ◽  
Young Infants ◽  
Resource Limited

Background: The effectiveness of antibiotics for the treatment of severe bacterial infections in newborns in resource-limited settings has been determined by empirical evidence. However, such an approach does not warrant optimal exposure to antibiotic agents, which are known to show different disposition characteristics in this population. Here we evaluate the rationale for a simplified regimen of gentamicin taking into account the effect of body size and organ maturation on pharmacokinetics. The analysis is supported by efficacy data from a series of clinical trials in this population.Methods: A previously published pharmacokinetic model was used to simulate gentamicin concentration vs. time profiles in a virtual cohort of neonates. Model predictive performance was assessed by supplementary external validation procedures using therapeutic drug monitoring data collected in neonates and young infants with or without sepsis. Subsequently, clinical trial simulations were performed to characterize the exposure to intra-muscular gentamicin after a q.d. regimen. The selection of a simplified regimen was based on peak and trough drug levels during the course of treatment.Results: In contrast to current World Health Organization guidelines, which recommend gentamicin doses between 5 and 7.5 mg/kg, our analysis shows that gentamicin can be used as a fixed dose regimen according to three weight-bands: 10 mg for patients with body weight <2.5 kg, 16 mg for patients with body weight between 2.5 and 4 kg, and 30 mg for those with body weight >4 kg.Conclusion: The choice of the dose of an antibiotic must be supported by a strong scientific rationale, taking into account the differences in drug disposition in the target patient population. Our analysis reveals that a simplified regimen is feasible and could be used in resource-limited settings for the treatment of sepsis in neonates and young infants with sepsis aged 0–59 days.

scholarly journals Nevirapine Exposure with WHO Pediatric Weight Band Dosing: Enhanced Therapeutic Concentrations Predicted Based on Extensive International Pharmacokinetic Experience

2012 ◽  
Vol 56 (10) ◽  
pp. 5374-5380 ◽  
Author(s):  
Mina Nikanjam ◽  
Desiré Kabamba ◽  
Tim R. Cressey ◽  
David Burger ◽  
Francesca T. Aweeka ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pharmacokinetic Model ◽  
Transcriptase Inhibitor ◽  
World Health ◽  
Fixed Dose ◽  
Target Range ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Resource Limited Settings ◽  
Resource Limited

ABSTRACTNevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used worldwide as part of combination antiretroviral therapy in infants and children to treat HIV infection. Dosing based on either weight or body surface area has been approved by the U.S. Food and Drug Administration (FDA) but can be difficult to implement in resource-limited settings. The World Health Organization (WHO) has developed simplified weight band dosing for NVP, but it has not been critically evaluated. NVP pharmacokinetic data were combined from eight pediatric clinical trials (Pediatric AIDS Clinical Trials Group [PACTG] studies 245, 356, 366, 377, 403, 1056, and 1069 and Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens [CHAPAS]) representing subjects from multiple continents and across the pediatric age continuum. A population pharmacokinetic model was developed to characterize developmental changes in NVP disposition, identify potential sources of NVP pharmacokinetic variability, and assess various pediatric dosing strategies and their impact on NVP exposure. Age, CYP2B6 genotype, and ritonavir were independent predictors of oral NVP clearance. The Triomune fixed-dose tablet was an independent predictor of bioavailability compared to the liquid and other tablet formulations. Monte Carlo simulations of the final model were used to assess WHO weight band dosing recommendations. The final pharmacokinetic model indicated that WHO weight band dosing is likely to result in a percentage of children with NVP exposure within the target range similar to that obtained with FDA dosing. Weight band dosing of NVP proposed by the WHO has the potential to provide a simple and effective dosing strategy for resource limited settings.

scholarly journals External validation of the predictive performance of population pharmacokinetic models for phenobarbital in pediatric patients

2020 ◽  
Author(s):  
Sunae Ryu ◽  
Woo Jin Jung ◽  
Zheng Jiao ◽  
Jung Woo Chae ◽  
Hwi-yeol Yun
Keyword(s):  
External Validation ◽  
Predictive Performance ◽  
Validation Dataset ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
Bayesian Forecasting ◽  
Predictive Capability ◽  
Young Infants ◽  
Simulation Based

Aim: Several studies have reported population pharmacokinetic models for phenobarbital (PB), but the predictive performance of these models has not been well documented. This study aims to do external validation of the predictive performance in published pharmacokinetic models. Methods: Therapeutic drug monitoring data collected in neonates and young infants treated with PB for seizure control, was used for external validation. A literature review was conducted through PubMed to identify population pharmacokinetic models. Prediction- and simulation-based diagnostics, and Bayesian forecasting were performed for external validation. The incorporation of size or maturity functions into the published models was also tested for prediction improvement. Results: A total of 79 serum concentrations from 28 subjects were included in the external validation dataset. Seven population pharmacokinetic studies of PB were selected for evaluation. The model by Voller et al. [27] showed the best performance concerning prediction-based evaluation. In simulation-based analyses, the normalized prediction distribution error of two models (those of Shellhaas et al. [24] and Marsot et al. [25]) obeyed a normal distribution. Bayesian forecasting with more than one observation improved predictive capability. Incorporation of both allometric size scaling and maturation function generally enhanced the predictive performance, but with marked improvement for the adult pharmacokinetic model. Conclusion: The predictive performance of published pharmacokinetic models of PB was diverse, and validation may be necessary to extrapolate to different clinical settings. Our findings suggest that Bayesian forecasting improves the predictive capability of individual concentrations for pediatrics.

scholarly journals A Scoping Review Protocol for Supply Chain Management Systems for Point of Care Diagnostics Services: Optimising COVID-19 Testing Capacity in Resource-limited Settings

2021 ◽  
Author(s):  
Kuhlula Maluleke ◽  
Thobeka Dlangalala ◽  
Alfred Musekiwa ◽  
Kabelo Kgarosi ◽  
Sphamandla Nkambule ◽  
...  
Keyword(s):  
Supply Chain ◽  
Supply Chain Management ◽  
Scoping Review ◽  
Point Of Care ◽  
Scientific Journal ◽  
World Health ◽  
Future Research ◽  
Resource Limited Settings ◽  
Chain Management ◽  
Resource Limited

Abstract BackgroundRapid and specific diagnostic tests are essential for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) testing to allow prompt isolation and early treatment initiation if necessary. Currently, reverse transcription polymerase chain reaction (RT-PCR) tests are the gold standard for SARS-CoV-2 testing but are difficult to implement in resource-limited settings with poor access to laboratory infrastructure. Point of care (POC) testing may be more feasible in resource-limited settings because POC testing is cost-effective, easy to perform, results are rapid, and they can be performed at all levels of healthcare by health professionals with minimal training. To ensure equitable access, it is important that SARS-CoV-2 testing is optimised through well-established supply chain management (SCM). Here we outline a protocol for a scoping review aimed at mapping literature on SCM for POC testing in resource limited settings to guide both future research and the implementation of SARS-CoV-2 POC diagnostics. MethodologyThis scoping review will be guided by an adapted version of the Arksey and O’Malley methodological framework. We will search the Medline Ovid, Medline EBSCO, Scopus, PubMed, PsychInfo, Web of Science and EBSCOHost databases. We will search gray literature in the form of dissertations/theses, conference proceedings, websites of international organisations such as the World Health Organisation and government reports. We will include articles reporting evidence published since inception. Language restrictions will not be applied. We will use a search summary table to test the effectiveness of the search strategy. Two reviewers will screen eligible studies using a tool developed for this scoping review. The quality of the included studies will be appraised using the mixed method appraisal tool (MMAT) version 2018. Discussion The proposed scoping review will gather relevant studies on SCM systems for POC diagnostics services globally. We anticipate that this review’s findings will guide future research on SCM systems for POC diagnostics services in resource-limited settings. The results will be published in a scientific journal, presented at relevant conferences and form part of workshops with key stakeholders involved in SCM systems for POC diagnostics services.

scholarly journals Characteristics of a Nationwide Voluntary Antibiotic Resistance Awareness Campaign in India; Future Paths and Pointers for Resource Limited Settings/Low and Middle Income Countries

2019 ◽  
Vol 16 (24) ◽  
pp. 5141
Author(s):  
Ashok J. Tamhankar ◽  
Ramesh Nachimuthu ◽  
Ravikant Singh ◽  
Jyoti Harindran ◽  
Gautam Kumar Meghwanshi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antibiotic Use ◽  
World Health ◽  
Awareness Campaign ◽  
Resource Limited Settings ◽  
Middle Income ◽  
Middle Income Countries ◽  
Awareness Campaigns ◽  
Resource Limited ◽  
Low And Middle Income

Antibiotic resistance has reached alarming proportions globally, prompting the World Health Organization to advise nations to take up antibiotic awareness campaigns. Several campaigns have been taken up worldwide, mostly by governments. The government of India asked manufacturers to append a ‘redline’ to packages of antibiotics as identification marks and conducted a campaign to inform the general public about it and appropriate antibiotic use. We investigated whether an antibiotic resistance awareness campaign could be organized voluntarily in India and determined the characteristics of the voluntarily organized campaign by administering a questionnaire to the coordinators, who participated in organizing the voluntary campaign India. The campaign characteristics were: multiple electro–physical pedagogical and participatory techniques were used, 49 physical events were organized in various parts of India that included lectures, posters, booklet/pamphlet distribution, audio and video messages, competitions, and mass contact rallies along with broadcast of messages in 11 local languages using community radio stations (CRS) spread all over India. The median values for campaign events were: expenditure—3000 Indian Rupees/day (US$~47), time for planning—1 day, program spread—4 days, program time—4 h, direct and indirect reach of the message—respectively 250 and 500 persons/event. A 2 min play entitled ‘Take antibiotics as prescribed by the doctor’ was broadcast 10 times/day for 5 days on CRS with listener reach of ~5 million persons. More than 85%ofcoordinators thought that the campaign created adequate awareness about appropriate antibiotic use and antibiotic resistance. The voluntary campaign has implications for resource limited settings/low and middle income countries.

scholarly journals Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants

2014 ◽  
Vol 59 (1) ◽  
pp. 482-489 ◽  
Author(s):  
Susanna E. Medellín-Garibay ◽  
Aída Rueda-Naharro ◽  
Silvia Peña-Cabia ◽  
Benito García ◽  
Silvia Romano-Moreno ◽  
...  
Keyword(s):  
Body Weight ◽  
Therapeutic Drug Monitoring ◽  
Population Pharmacokinetics ◽  
Drug Monitoring ◽  
Pediatric Population ◽  
External Validation ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Time Data ◽  
Age Related

ABSTRACTThe aim of this study was to characterize and validate the population pharmacokinetics of gentamicin in infants and to determine the influences of clinically relevant covariates to explain the inter- and intraindividual variabilities associated with this drug. Infants receiving intravenous gentamicin and with routine therapeutic drug monitoring were consecutively enrolled in the study. Plasma concentration and time data were retrospectively collected from 208 infants (1 to 24 months old) of the Hospital Universitario Severo Ochoa (Spain), of whom 44% were males (mean age [± standard deviation], 5.8 ± 4.8 months; mean body weight, 6.4 ± 2.2 kg). Data analysis was performed with NONMEM 7.2. One- and two-compartment open models were analyzed to estimate the gentamicin population parameters and the influences of several covariates. External validation was carried out in another population of 55 infants. The behavior of gentamicin in infants exhibits two-compartment pharmacokinetics, with total body weight being the covariate that mainly influences central volume (Vc) and clearance (CL); this parameter was also related to creatinine clearance. Both parameters are age related and different from those reported for neonatal populations. On the basis of clinical presentation and diagnosis, a once-daily dosage regimen of 7 mg/kg of body weight every 24 h is proposed for intravenous gentamicin, followed by therapeutic drug monitoring in order to avoid toxicity and ensure efficacy with minimal blood sampling. Gentamicin pharmacokinetics and disposition were accurately characterized in this pediatric population (infants), with the parameters obtained being different from those reported for neonates and children. These differences should be considered in the dosing and therapeutic monitoring of this antibiotic.

scholarly journals Prescribing Patterns of Aminoglycoside Antibiotics in a Teaching Hospital in Sudan

2020 ◽  
pp. 1-5
Author(s):  
Abduelmula Abduelkarem ◽  
Abduelmula Abduelkarem ◽  
Einas A Bakheit ◽  
Kamal M Elhag
Keyword(s):  
Body Weight ◽  
Bacterial Infections ◽  
Laboratory Data ◽  
Ideal Body Weight ◽  
University Hospital ◽  
Prescribing Patterns ◽  
Therapeutic Drug ◽  
Sensitivity Testing ◽  
Inappropriate Use ◽  
Ideal Body

Background: Aminoglycoside antimicrobials are widely used for the treatment of severe gram-negative bacterial infections. Their inappropriate use may result in treatment failure, development of resistant pathogens, and toxicity. Drug utilization evaluation of aminoglycosides can improve rational use. Purpose: This study intended to assess the prescribing patterns and potential problems associated with gentamicin and amikacin use. Methods: This prospective observational study was conducted at Soba University Hospital, Khartoum, Sudan. Patients’ demographics, clinical and prescription information were collected using a data collection form. Laboratory data of patients were collected from the patients' files. Ideal body weight was calculated to assess dose appropriateness, and adverse drug reactions were observed. Results: A total of 200 patients were included in the present study, two-thirds of the patients were prescribed gentamicin, while the remainder were given amikacin. Dosing was inappropriate in (60.6%) and (76.5%) of patients on gentamicin and amikacin respectively. Conventional dosing was used more commonly (67%) than extended dosing (33%). All indications for the use of these drugs were found to be appropriate. In (72%) of cases, both gentamicin and amikacin were prescribed based on microbiological sensitivity testing. Auditory function monitoring was only performed for neonates and infants. Nephrotoxicity was detected in 7 patients (9.3%), and ototoxicity in one patient (1.3%). Conclusion: Although prescription and dosing based on ideal body weight and microbiological data were reasonably common, higher compliance with recommended practice is needed in addition to therapeutic drug monitoring in order to ensure safe and effective treatment, and reduced antibiotic resistance.

scholarly journals EDITORIAL: COVID-19: Rebooting pharmacy education in resource-limited settings

2021 ◽  
pp. 67-70
Author(s):  
Jennie Lates ◽  
Dan Kibuule
Keyword(s):  
Health Systems ◽  
World Health Organisation ◽  
Pharmacy Education ◽  
Sub Saharan Africa ◽  
World Health ◽  
Resource Limited Settings ◽  
Non Communicable Diseases ◽  
High Burden ◽  
Resource Limited ◽  
Sub Saharan

Globally, the COVID-19 pandemic has aggravated inequalities in access to quality pharmacy education, particularly in resource-limited settings in Africa (Engle, 2020; Fuller et al., 2020). This is a serious concern for Africa especially, given that sub-Saharan Africa ranks lowest on the global pharmaceutical workforce index and has a disproportionately high burden of infectious and non-communicable diseases, combined with weak health systems (World Health Organisation [WHO], 2013; Bates et al., 2018).

Sign in / Sign up

Export Citation Format

Share Document