Ceftazidime stability and pyridine toxicity during continuous i.v. infusion

Jones, Terry E.; Selby, P.; Mellor, Coby S; Cheam, Dat Boon

doi:10.1093/ajhp/zxy035

Cited by 21 publications

(15 citation statements)

References 18 publications

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“…The daily exposure limit of pyridine in humans is set at 2 mg by the European Medicines Agency and United States Pharmacopeia. 13 Humans are exposed to pyridine every day through the environment and their diet. 13 Also, a small amount of residual pyridine is present in pharmaceuticals as it is commonly used as a production solvent.…”

Section: Discussionmentioning

confidence: 99%

“…13 Humans are exposed to pyridine every day through the environment and their diet. 13 Also, a small amount of residual pyridine is present in pharmaceuticals as it is commonly used as a production solvent. In fact, a small but not quantifiable peak of pyridine was observed when unstressed ceftazidime was analysed using the HPLC method (Figure 1(a)), suggesting the presence of pyridine in the commercially available ceftazidime formulation.…”

Section: Discussionmentioning

confidence: 99%

“…3 Depending on the type of dosing, as well as dwell time, ceftazidime can remain in the peritoneal cavity for 4-10 h. Ceftazidime is a relatively unstable compound and upon degradation, one by-product is the potentially toxic pyridine. 5 The rate of pyridine generation depends on the initial concentration of ceftazidime, pH of the solution and storage temperature. [6][7][8] The possible toxic effects of pyridine in humans include neurotoxicity, liver disorders, with possibly carcinogenic effects observed in animal models.…”

Section: Introductionmentioning

confidence: 99%

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Pyridine levels in ceftazidime – peritoneal dialysis admixtures stored at body temperature

et al. 2020

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Background: For the treatment of peritoneal dialysis-associated peritonitis (PDAP), ceftazidime is routinely admixed with peritoneal dialysis (PD) solutions before its intraperitoneal administration. One of the major degradation products of ceftazidime is pyridine, a potentially toxic compound. Depending on the type of PD solution, ceftazidime is exposed to an environment with acidic or basic pH, and depending on the type of dosing and individual unit practices related to preparation and storage, ceftazidime can be at body temperature for 4–10 h, resulting in potentially varying rates of degradation to pyridine by-product. No study has investigated whether the amount of generated pyridine exceeds the maximum daily exposure limit of 2 mg when ceftazidime-PD admixtures are kept at body temperature. Therefore, the current study aimed to determine the levels of pyridine generated in PD-ceftazidime admixtures kept at 37°C for various time points. Methods: Ceftazidime was admixed with 2 L Dianeal (1.5%, 2.5% and 4.25% dextrose) and 2 L Physioneal (1.36%, 2.27% and 3.86% glucose) PD solutions to obtain a concentration of 125 mg/L (continuous dosing model) or 500 mg/L (intermittent dosing model). A total of 36 PD admixtures (3 bags for each type of PD solution and 3 bags for each type of dosing) were prepared and stored at 37°C for 10 h. An aliquot was withdrawn at time 0 (baseline) and after 2, 6, 8 and 10 h of storage. The withdrawn samples were then analysed to determine the concentrations of ceftazidime and pyridine using high-performance liquid chromatography. Results: With the intermittent dosing model (500 mg/L), ceftazidime was found to be stable for only 2 and 6 h when admixed with 3.86% and 2.27% glucose Physioneal PD solutions, respectively. While ceftazidime (500 mg/L) retained more than 90% of its initial concentration in the three types of Dianeal and 1.36% dextrose Physioneal solutions for 10 and 8 h, respectively, the generated amount of pyridine ranged between approximately 290% and 371% more than the daily recommended limit. With the continuous dosing model (125 mg/L), ceftazidime was found to be stable for 6 h in all three types of Physioneal PD solutions, but the total amount of generated pyridine with four daily exchanges (6 h each) was estimated to be 170–360% over the daily recommended limit. Ceftazidime (125 mg/L) was chemically stable when admixed with three types of Dianeal PD solutions and stored at 37°C for 10 h, and the levels of pyridine were estimated to be less than the maximum recommended daily limit. Conclusions: Until the outcomes of this in vitro study are confirmed by appropriate in vivo studies, continuous dosing of ceftzadime–Dianeal admixtures for the treatment of PDAP may be preferred over continuous dosing of ceftazidime–Physioneal admixtures, and intermittent dosing of ceftazidime–Physioneal and ceftazidime–Dianeal admixtures, as ceftazidime remains stable and the generated levels of pyridine are below the maximum recommended daily exposure.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pyridine levels in ceftazidime – peritoneal dialysis admixtures stored at body temperature

et al. 2020

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“…Esto ha llevado a la implementación de regímenes de administración que consisten en la prolongación del tiempo de infusión o el uso de infusiones continuas de 24 h 48 . No obstante, este enfoque no está exento de complicaciones dado que, la estabilidad en uso de algunos antimicrobianos a distintas temperaturas, concentraciones y diluyentes podría influir negativamente sobre la degradación del fármaco o producción de compuestos tóxicos y llevar a una reducción en la efectividad, tal como se ha planteado para ceftazidima 49 . La Tabla 3, muestra las estabilidades de algunos antimicrobianos a distintas temperaturas y concentraciones 50 .…”

Section: Estabilidad En Usounclassified

Antimicrobianos en neonatología. Parte II: Recomendaciones para la dilución y administración de antimicrobianos utilizados en el recién nacido

et al. 2021

Rev. chil. infectol.

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Antimicrobials are among the most commonly prescribed classes of medications in Neonatal Intensive Care Units; however, its use has been constantly associated with a number of medication errors in clinical practice. In contrast to this situation, there is no common agreement when it comes to determining the right dosing, administration, or handling of antibiotics in this population. In order to help improve the use of antibiotics, decrease the rate of medication errors and optimize clinical results in the newborn, this review aims to provide recommendations to support and guide the correct preparation of some of the most relevant antibiotics used in neonatal wards.

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“…As for continuous infusion ceftazidime for the treatment of outpatients, Jones et al demonstrated its safe and effective use with once-daily changes of infusion device, provided the concentration and temperature of the infusion solution is controlled, in order to limit its degradation and pyridine formation [68].…”

Section: Clinical Outcomementioning

confidence: 99%

Optimizing Antibiotic Treatment Strategies for Neonates and Children: Does Implementing Extended or Prolonged Infusion Provide any Advantage?

et al. 2020

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Optimizing the use of antibiotics has become mandatory, particularly for the pediatric population where limited options are currently available. Selecting the dosing strategy may improve overall outcomes and limit the further development of antimicrobial resistance. Time-dependent antibiotics optimize their free concentration above the minimal inhibitory concentration (MIC) when administered by continuous infusion, however evidences from literature are still insufficient to recommend its widespread adoption. The aim of this review is to assess the state-of-the-art of intermittent versus prolonged intravenous administration of antibiotics in children and neonates with bacterial infections. We identified and reviewed relevant literature by searching PubMed, from 1 January 1 2000 to 15 April 2020. We included studies comparing intermittent versus prolonged/continuous antibiotic infusion, among the pediatric population. Nine relevant articles were selected, including RCTs, prospective and retrospective studies focusing on different infusion strategies of vancomycin, piperacillin/tazobactam, ceftazidime, cefepime and meropenem in the pediatric population. Prolonged and continuous infusions of antibiotics showed a greater probability of target attainment as compared to intermittent infusion regimens, with generally good clinical outcomes and safety profiles, however its impact in terms on efficacy, feasibility and toxicity is still open, with few studies led on children and adult data not being fully extendable.

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Ceftazidime stability and pyridine toxicity during continuous i.v. infusion

Cited by 21 publications

References 18 publications

Pyridine levels in ceftazidime – peritoneal dialysis admixtures stored at body temperature

Pyridine levels in ceftazidime – peritoneal dialysis admixtures stored at body temperature

Antimicrobianos en neonatología. Parte II: Recomendaciones para la dilución y administración de antimicrobianos utilizados en el recién nacido

Optimizing Antibiotic Treatment Strategies for Neonates and Children: Does Implementing Extended or Prolonged Infusion Provide any Advantage?

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