Is continuous infusion ceftriaxone better than once-a-day dosing in intensive care? A randomized controlled pilot study

Roberts, Jason A.; Rickard, Claire M; Thomas, Peter J.; Quinn, Jo; Roberts, Darren M.; Richards, Brent; Lipman, Jeffrey

doi:10.1093/jac/dkl478

Cited by 117 publications

(129 citation statements)

References 32 publications

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“…Clinical cure was also higher in the continuous infusion group (70% vs. 43%, p=0.037); however, there was no observed difference in survival. These observations are similar to other small non-randomized studies that reported greater clinical success rates with continuous infusion piperacillin/tazobactam, meropenem, and ceftriaxone versus that of standard infusion in critically ill patients [60][61][62]. Finally, a doubleblind, randomized controlled study of doripenem 500 mg q8h as a 4 hour prolonged infusion versus standard infusion imipenem-cilastatin in patients with ventilator-associated pneumonia demonstrated noninferiority between dosing regimens; however, clinical success against the small population of patients infected with P. aeruginosa was numerically in favor of the prolonged infusion regimen [80% (16/20) vs. 43% (6/14)] [63].…”

Section: β-Lactamssupporting

confidence: 88%

Optimizing Antibiotic Pharmacodynamics for Clinical Practice

Connors

Kuti²,

Nicolau³

2013

Pharmaceut Anal Acta

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Section: β-Lactamssupporting

confidence: 88%

Optimizing Antibiotic Pharmacodynamics for Clinical Practice

Connors

Kuti²,

Nicolau³

2013

Pharmaceut Anal Acta

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“…A 3-h infusion of meropenem was reported to give a higher TϾMIC in plasma than a bolus injection (14). In addition, several clinical studies have suggested that prolonged infusion of beta-lactams offers clinical and bacteriological advantages for critically ill patients, including those with pulmonary infections (15,21,22,26). However, little is known about the PK/PD profile of beta-lactams in bronchial ELF and how well these drugs penetrate into bronchial regions when given intravenously by prolonged infusion.…”

mentioning

confidence: 99%

Comparison of the Pharmacodynamics of Biapenem in Bronchial Epithelial Lining Fluid in Healthy Volunteers Given Half-Hour and Three-Hour Intravenous Infusions

Kikuchi

Nasuhara

et al. 2009

Antimicrob Agents Chemother

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The time above the MIC (T>MIC) is the pharmacokinetic/pharmacodynamic (PK/PD) parameter that correlates with the therapeutic efficacy of beta-lactam antibiotics. A prolonged infusion can provide plasma drug concentrations that remain above the MIC for a long period. The objective of this study was to compare the PK/PD parameters in bronchial epithelial lining fluid (ELF) of biapenem given as 0.5-h and 3-h infusions by using bronchoscopic microsampling (BMS). Six healthy adult volunteers received 0.5-h and 3-h infusions of 0.3 g of biapenem with a washout interval. BMS was performed repeatedly from 0.5 to 24 h after biapenem administration in order to determine the pharmacokinetics in bronchial ELF. The subjects received intravenous biapenem with the same regimens again and then underwent bronchoalveolar lavage (BAL) at the end of infusion in order to determine the concentration of the drug in alveolar ELF. The percentages (means ؎ standard deviations) of T>MIC in bronchial ELF at MICs from 0.25 to 4 g/ml ranged from zero to 34.6% ؎ 5.2% after the 0.5-h infusion and from 5.1% ؎ 5.6% to 52.2% ؎ 17.0% after the 3-h infusion. The percentage of T>MIC in bronchial ELF after the 3-h infusion tended to be higher than that after the 0.5-h infusion. The concentrations of the drug in alveolar ELF after 0.5-h and 3-h infusions were 3.5 ؎ 1.2 g/ml and 1.3 ؎ 0.3 g/ml, respectively. The present results support the use of prolonged infusions of beta-lactam antibiotics and may provide critical information for successful treatment of lower respiratory tract infections based on PK/PD parameters in bronchial ELF.

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“…Growing evidence suggests that optimised antibiotic dosing in severely septic patients can increase clinical cure rates and reduce mortality (6)(7)(8). To develop such dosing regimens, detailed knowledge of the antibiotic's PK is required.…”

Section: Overviewmentioning

confidence: 99%

“…Moreover, there is growing evidence which demonstrates the optimisation of antibiotic dosing in accordance with its PK/PD profile increases clinical cure rates and reduces mortality, especially in severely septic patients (6,7,(34)(35)(36)(37).…”

Section: Antibiotic Pk/pdmentioning

confidence: 99%

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Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

Tsai¹

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Sepsis is a major health issue in the Australian Indigenous population. Unfortunately, the high rates of mortality and morbidity caused by sepsis or severe sepsis in this population have not significantly reduced over recent decades. Research into the role of optimisation of antibiotic therapy for improving patient outcomes is certainly an important area of need. In other patient populations, there is increasing evidence of an improvement of clinical cure rates and survival in patients with severe sepsis when antibiotic dosing results in therapeutic concentrations, that is, achieves pharmacokinetic/pharmacodynamic (PK/PD) targets. However, numerous PK changes caused by the altered physiology associated with critical illness may reduce the likelihood of such effective dosing.Previous studies have identified a number of physiological characteristics in the Australian Indigenous population which suggest that interethnic PK differences are likely in comparison with the non-Indigenous. As most PK data of antibiotics were obtained from healthy Caucasian volunteers, whether these data can be extrapolated to the critically ill Indigenous patients requires investigation.The aims of this thesis are to describe the PK of meropenem, ceftriaxone, vancomycin and piperacillin in severely septic Indigenous patients; compare the PK with existing data from nonIndigenous patients; design optimised dosing regimens for each of the study antibiotics; and quantify the variation in renal function of critically ill Indigenous patients. This thesis consists of nine Chapters:Chapter one provides an overview of the current clinical challenges encountered in antibiotic dosing in critically ill patients. It also discusses specific physiological characteristics of Australian Indigenous patients which may lead to different PK compared with non-Indigenous comparators.Chapter two comprises of a narrative review which discusses the PK/PD factors that should be considered when prescribing antibiotics to critically ill patients. This Chapter summarises data which describe an improvement in clinical outcome when antibiotics achieve PK/PD targets. ThisChapter concludes to support an individualised approach to dosing antibiotics as opposed to the 'one dose fits all' approach that is common to clinical practice.ii Chapter three incorporates a systematic review which investigates the published data describing differences in antibiotic PK between different ethnic groups. No reports on PK in Indigenous Australians were found. The predominant data described differences in PK between the Asian and Caucasian ethnicities. Typically, Asian subjects manifested higher antibiotic concentrations for antibiotics that have significant hepatic metabolism, are substrates to p-glycoprotein or other forms of active transport and/or have high alpha-1-acid glycoprotein binding.Chapter four incorporates a study which described the renal function of critically ill Australian Indigenous patients. This study found a numerically higher incidence of augmented renal clea...

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Is continuous infusion ceftriaxone better than once-a-day dosing in intensive care? A randomized controlled pilot study

Cited by 117 publications

References 32 publications

Optimizing Antibiotic Pharmacodynamics for Clinical Practice

Optimizing Antibiotic Pharmacodynamics for Clinical Practice

Comparison of the Pharmacodynamics of Biapenem in Bronchial Epithelial Lining Fluid in Healthy Volunteers Given Half-Hour and Three-Hour Intravenous Infusions

Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

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