The Journal of antimicrobial chemotherapy
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J. Antimicrob. Chemother. · Oct 2019
Development of pyridyl thiosemicarbazones as highly potent agents for the treatment of malaria after oral administration.
Drug resistance exists to all current and investigational antimalarial drug classes. Consequently, we have set out to develop chemically and mechanistically discrete antimalarials. Here we report on the development of thiosemicarbazone (TSC) antimalarials, with TSC3 as the most advanced lead. ⋯ TSC3 shows promise as a persistent, potent and orally effective antimalarial. This, coupled with the extremely low cost of synthesis, suggests that the further development of antimalarial thiosemicarbazones is clearly warranted.
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J. Antimicrob. Chemother. · Oct 2019
Observational StudyOptimized meropenem dosage regimens using a pharmacokinetic/pharmacodynamic population approach in patients undergoing continuous venovenous haemodiafiltration with high-adsorbent membrane.
The pharmacokinetics (PK) of antibiotics change during sepsis and continuous renal replacement therapies in critically ill patients. Limited evidence exists on the use of the oXiris® high-adsorbent membrane. ⋯ We have constructed a PK model of meropenem in sepsis patients undergoing CVVHDF using the oXiris® membrane. This tool will support physicians when calculating the optimal initial dose.
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J. Antimicrob. Chemother. · Oct 2019
Establishing a baseline for a national paediatric antimicrobial stewardship programme.
The majority of antimicrobial stewardship programmes focus on prescribing in adult populations; however, there is a recognized need for targeted paediatric antimicrobial stewardship to improve the quality and safety of prescribing amongst this patient group. ⋯ Data from national prevalence surveys are advantageous when developing antimicrobial stewardship programmes. Results have highlighted differences in the prescribing landscape between paediatric inpatient populations in specialist hospitals and acute hospitals, and have informed priorities for the national antimicrobial stewardship programme, which reinforces the need for a targeted paediatric antimicrobial stewardship programme.
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J. Antimicrob. Chemother. · Oct 2019
Studies of selective digestive decontamination as a natural experiment to evaluate topical antibiotic prophylaxis and cephalosporin use as population-level risk factors for enterococcal bacteraemia among ICU patients.
Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) regimens appear protective against ICU-acquired overall bacteraemia. These regimens can be factorized as topical antibiotic prophylaxis (TAP) with (SDD) or without (SOD) protocolized parenteral antibiotic prophylaxis (PPAP) using cephalosporins. Both TAP and cephalosporins are risk factors for enterococcal colonization although their impact on enterococcal bacteraemia within studies of SDD/SOD remains unclear. ⋯ The incidences of enterococcal bacteraemia within both concurrent control and intervention groups of SDD/SOD studies are unusually high compared with the literature-derived benchmark. The impact of parenteral cephalosporin used as PPAP additional to TAP on enterococcal bacteraemia incidence was indeterminate in this analysis.