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Anita K M Zaidi - One of the best experts on this subject based on the ideXlab platform.
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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
The Lancet Global Health, 2017Co-Authors: Fatima Mir, Imran Nisar, Shiyam Sundar Tikmani, Benazir Baloch, Sadia Shakoor, Fyezah Jehan, Imran Ahmed, Simon Cousens, Anita K M ZaidiAbstract:Summary 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.
Andrew Henderson - One of the best experts on this subject based on the ideXlab platform.
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Benzylpenicillin versus flucloxacillin for penicillin susceptible staphylococcus aureus bloodstream infections from a large retrospective cohort study
International Journal of Antimicrobial Agents, 2019Co-Authors: John D. Turnidge, Andrew Henderson, Patrick N A Harris, Gunter Hartel, David L Paterson, Joshua S Davis, Steven Y. C. TongAbstract:ABSTRACT In clinical practice, differing opinions exists regarding the optimal management of patients with penicillin-susceptible Staphylococcus aureus (PSSA) bloodstream infection (BSI). The aim of this study was to compare the 30-day mortality of patients treated with Benzylpenicillin or flucloxacillin for PSSA BSI from a large prospectively collected data set from Australia and New Zealand. A logistic regression model and propensity score treatment analysis using inverse probability of treatment weighting were used. A total of 915 patients were included in the study, with an overall mortality rate of 12.9% (118/915) [Benzylpenicillin 10.5% (33/315) and flucloxacillin 14.2% (85/600)]. Endocarditis was associated with Benzylpenicillin treatment choice, whereas skin and soft-tissue infection was associated with flucloxacillin treatment choice. In the multivariate analysis, increased 30-day mortality was associated with flucloxacillin compared with Benzylpenicillin [odds ratio (OR) = 1.6, 95% confidence interval (CI) 1.0–2.5; P = 0.05). When adjusted for treatment choice in the propensity score analysis, flucloxacillin was again associated with increased 30-day mortality (OR = 1.06, 95% CI 1.01–1.1; P = 0.03). An increase in 30-day mortality associated with flucloxacillin use suggests a potential benefit for Benzylpenicillin therapy in patients with PSSA BSI.
Steven Y. C. Tong - One of the best experts on this subject based on the ideXlab platform.
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Benzylpenicillin versus flucloxacillin for penicillin susceptible staphylococcus aureus bloodstream infections from a large retrospective cohort study
International Journal of Antimicrobial Agents, 2019Co-Authors: John D. Turnidge, Andrew Henderson, Patrick N A Harris, Gunter Hartel, David L Paterson, Joshua S Davis, Steven Y. C. TongAbstract:ABSTRACT In clinical practice, differing opinions exists regarding the optimal management of patients with penicillin-susceptible Staphylococcus aureus (PSSA) bloodstream infection (BSI). The aim of this study was to compare the 30-day mortality of patients treated with Benzylpenicillin or flucloxacillin for PSSA BSI from a large prospectively collected data set from Australia and New Zealand. A logistic regression model and propensity score treatment analysis using inverse probability of treatment weighting were used. A total of 915 patients were included in the study, with an overall mortality rate of 12.9% (118/915) [Benzylpenicillin 10.5% (33/315) and flucloxacillin 14.2% (85/600)]. Endocarditis was associated with Benzylpenicillin treatment choice, whereas skin and soft-tissue infection was associated with flucloxacillin treatment choice. In the multivariate analysis, increased 30-day mortality was associated with flucloxacillin compared with Benzylpenicillin [odds ratio (OR) = 1.6, 95% confidence interval (CI) 1.0–2.5; P = 0.05). When adjusted for treatment choice in the propensity score analysis, flucloxacillin was again associated with increased 30-day mortality (OR = 1.06, 95% CI 1.01–1.1; P = 0.03). An increase in 30-day mortality associated with flucloxacillin use suggests a potential benefit for Benzylpenicillin therapy in patients with PSSA BSI.
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short course oral co trimoxazole versus intramuscular benzathine Benzylpenicillin for impetigo in a highly endemic region an open label randomised controlled non inferiority trial
The Lancet, 2014Co-Authors: Asha C. Bowen, Irene M Omeara, Mark D. Chatfield, Ross M Andrews, Malcolm Mcdonald, Bart J. Currie, Steven Y. C. Tong, Jonathan R CarapetisAbstract:Summary Background Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance. Few trials of systemic antibiotics are available to guide management of extensive impetigo. As such, we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine Benzylpenicillin in children with impetigo in a highly endemic setting. Methods In this randomised, controlled, non-inferiority trial, Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned (1:1:1) to receive benzathine Benzylpenicillin (weight-banded injection), twice-daily co-trimoxazole for 3 days (4 mg/kg plus 20 mg/kg per dose), or once-daily co-trimoxazole for 5 days (8 mg/kg plus 40 mg/kg per dose). At every visit, participants were randomised in blocks of six and 12, stratified by disease severity. Randomisation was done by research nurses and codes were in sealed, sequentially numbered, opaque envelopes. Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7. The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000858291. Findings Between Nov 26, 2009, and Nov 20, 2012, 508 patients were randomly assigned to receive benzathine Benzylpenicillin (n=165 [156 analysed]), twice-daily co-trimoxazole for 3 days (n=175 [173 analysed]), or once-daily co-trimoxazole for 5 days (n=168 [161 analysed]). Treatment was successful in 133 (85%) children who received benzathine Benzylpenicillin and 283 (85%) who received pooled co-trimoxazole (absolute difference 0·5%; 95% CI −6·2 to 7·3), showing non-inferiority of co-trimoxazole (10% margin). Results for twice-daily co-trimoxazole for 3 days and once-daily co-trimoxazole for 5 days were similar. Adverse events occurred in 54 participants, 49 (90%) of whom received benzathine Benzylpenicillin. Interpretation Short-course co-trimoxazole is a non-inferior, alternative treatment to benzathine Benzylpenicillin for impetigo; it is palatable, pain-free, practical, and easily administered. Funding Australian National Health and Medical Research Council.
Asha C. Bowen - One of the best experts on this subject based on the ideXlab platform.
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a population pharmacokinetic study of benzathine Benzylpenicillin g administration in children and adolescents with rheumatic heart disease new insights for improved secondary prophylaxis strategies
Journal of Antimicrobial Chemotherapy, 2019Co-Authors: Robert Hand, Nelly Newall, Julie Vine, Amy Baker, Madhu Pagesharp, Sam Salman, Katherine Gray, Asha C. Bowen, Joseph KadoAbstract:BACKGROUND Benzathine Benzylpenicillin G (BPG) is recommended as secondary prophylaxis to prevent recurrence of acute rheumatic fever and subsequent rheumatic heart disease (RHD). Following intramuscular injection, BPG is hydrolysed to Benzylpenicillin. Little is known of the pharmacokinetics of Benzylpenicillin following BPG in populations at risk of RHD. METHODS We conducted a longitudinal pharmacokinetic study of children and adolescents receiving secondary prophylaxis throughout six monthly cycles of BPG. Dried blood spot samples were assayed with LC-MS/MS. Benzylpenicillin concentrations were analysed using non-linear mixed-effects modelling with subsequent simulations based on published BMI-for-age and weight-for-age data. RESULTS Eighteen participants contributed 256 concentrations for analysis. None had Benzylpenicillin concentrations >0.02 mg/L for the full time between doses. The median duration above this target was 9.8 days for those with a lower BMI ( 0.02 mg/L for the majority of the time between injections. The discordance of this observation with reported efficacy of BPG to prevent rheumatic fever implies a major knowledge gap relating to pharmacokinetic/pharmacodynamic relationships between Benzylpenicillin exposure and clinical outcomes.
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a population pharmacokinetic study of benzathine Benzylpenicillin g administration in children and adolescents with rheumatic heart disease new insights for improved secondary prophylaxis strategies
Journal of Antimicrobial Chemotherapy, 2019Co-Authors: Robert Hand, Nelly Newall, Julie Vine, Amy Baker, Madhu Pagesharp, Sam Salman, Katherine Gray, Asha C. Bowen, Joseph KadoAbstract:Background Benzathine Benzylpenicillin G (BPG) is recommended as secondary prophylaxis to prevent recurrence of acute rheumatic fever and subsequent rheumatic heart disease (RHD). Following intramuscular injection, BPG is hydrolysed to Benzylpenicillin. Little is known of the pharmacokinetics of Benzylpenicillin following BPG in populations at risk of RHD.
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short course oral co trimoxazole versus intramuscular benzathine Benzylpenicillin for impetigo in a highly endemic region an open label randomised controlled non inferiority trial
The Lancet, 2014Co-Authors: Asha C. Bowen, Irene M Omeara, Mark D. Chatfield, Ross M Andrews, Malcolm Mcdonald, Bart J. Currie, Steven Y. C. Tong, Jonathan R CarapetisAbstract:Summary Background Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance. Few trials of systemic antibiotics are available to guide management of extensive impetigo. As such, we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine Benzylpenicillin in children with impetigo in a highly endemic setting. Methods In this randomised, controlled, non-inferiority trial, Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned (1:1:1) to receive benzathine Benzylpenicillin (weight-banded injection), twice-daily co-trimoxazole for 3 days (4 mg/kg plus 20 mg/kg per dose), or once-daily co-trimoxazole for 5 days (8 mg/kg plus 40 mg/kg per dose). At every visit, participants were randomised in blocks of six and 12, stratified by disease severity. Randomisation was done by research nurses and codes were in sealed, sequentially numbered, opaque envelopes. Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7. The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000858291. Findings Between Nov 26, 2009, and Nov 20, 2012, 508 patients were randomly assigned to receive benzathine Benzylpenicillin (n=165 [156 analysed]), twice-daily co-trimoxazole for 3 days (n=175 [173 analysed]), or once-daily co-trimoxazole for 5 days (n=168 [161 analysed]). Treatment was successful in 133 (85%) children who received benzathine Benzylpenicillin and 283 (85%) who received pooled co-trimoxazole (absolute difference 0·5%; 95% CI −6·2 to 7·3), showing non-inferiority of co-trimoxazole (10% margin). Results for twice-daily co-trimoxazole for 3 days and once-daily co-trimoxazole for 5 days were similar. Adverse events occurred in 54 participants, 49 (90%) of whom received benzathine Benzylpenicillin. Interpretation Short-course co-trimoxazole is a non-inferior, alternative treatment to benzathine Benzylpenicillin for impetigo; it is palatable, pain-free, practical, and easily administered. Funding Australian National Health and Medical Research Council.
Joseph Kado - One of the best experts on this subject based on the ideXlab platform.
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a population pharmacokinetic study of benzathine Benzylpenicillin g administration in children and adolescents with rheumatic heart disease new insights for improved secondary prophylaxis strategies
Journal of Antimicrobial Chemotherapy, 2019Co-Authors: Robert Hand, Nelly Newall, Julie Vine, Amy Baker, Madhu Pagesharp, Sam Salman, Katherine Gray, Asha C. Bowen, Joseph KadoAbstract:Background Benzathine Benzylpenicillin G (BPG) is recommended as secondary prophylaxis to prevent recurrence of acute rheumatic fever and subsequent rheumatic heart disease (RHD). Following intramuscular injection, BPG is hydrolysed to Benzylpenicillin. Little is known of the pharmacokinetics of Benzylpenicillin following BPG in populations at risk of RHD.
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a population pharmacokinetic study of benzathine Benzylpenicillin g administration in children and adolescents with rheumatic heart disease new insights for improved secondary prophylaxis strategies
Journal of Antimicrobial Chemotherapy, 2019Co-Authors: Robert Hand, Nelly Newall, Julie Vine, Amy Baker, Madhu Pagesharp, Sam Salman, Katherine Gray, Asha C. Bowen, Joseph KadoAbstract:BACKGROUND Benzathine Benzylpenicillin G (BPG) is recommended as secondary prophylaxis to prevent recurrence of acute rheumatic fever and subsequent rheumatic heart disease (RHD). Following intramuscular injection, BPG is hydrolysed to Benzylpenicillin. Little is known of the pharmacokinetics of Benzylpenicillin following BPG in populations at risk of RHD. METHODS We conducted a longitudinal pharmacokinetic study of children and adolescents receiving secondary prophylaxis throughout six monthly cycles of BPG. Dried blood spot samples were assayed with LC-MS/MS. Benzylpenicillin concentrations were analysed using non-linear mixed-effects modelling with subsequent simulations based on published BMI-for-age and weight-for-age data. RESULTS Eighteen participants contributed 256 concentrations for analysis. None had Benzylpenicillin concentrations >0.02 mg/L for the full time between doses. The median duration above this target was 9.8 days for those with a lower BMI ( 0.02 mg/L for the majority of the time between injections. The discordance of this observation with reported efficacy of BPG to prevent rheumatic fever implies a major knowledge gap relating to pharmacokinetic/pharmacodynamic relationships between Benzylpenicillin exposure and clinical outcomes.