Limitations of ceftriaxone compared with cefazolin against MSSA: an integrated pharmacodynamic analysis

Zelenitsky, Sheryl; Beahm, Nathan P; Iacovides, Harris; Ariano, Robert E.; Zhanel, George G.

doi:10.1093/jac/dky120

Cited by 18 publications

(7 citation statements)

References 27 publications

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“…They have multiple targets complicating interpretation of these findings. For example, ceftriaxone inhibits penicillin-binding proteins on the inner membrane of the bacterial cell wall and N-acetylcysteine increases glutathione production (Atkuri et al, 2007;Zelenitsky et al, 2018). Furthermore, ceftriaxone-induced upregulation of GLT-1 expression does not necessarily translate to accelerated glutamate uptake, as one report found that ceftriaxone application had no effect on basal and activity-dependent glutamate clearance (Wilkie et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Elevation of Extracellular Glutamate by Blockade of Astrocyte Glutamate Transporters Inhibits Cocaine Reinforcement in Rats via a NMDA-GluN2B Receptor Mechanism

Yang

Hempel

et al. 2022

J. Neurosci.

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It is well established that glutamate plays an important role in drug-induced and cue-induced reinstatement of drug seeking. However, the role of glutamate in drug reward is unclear. In this study, we systemically evaluated the effects of multiple glutamate transporter (GLT) inhibitors on extracellular glutamate and dopamine (DA) in the nucleus accumbens (NAc), intravenous cocaine self-administration, intracranial brain-stimulation reward (BSR), and reinstatement of cocaine seeking in male and female rats. Among the five GLT inhibitors we tested, TFB-TBOA was the most potent. Microinjections of TFB-TBOA into the NAc, but not the ventral tegmental area (VTA), or dorsal striatum (DS), dose-dependently inhibited cocaine selfadministration under fixed-ratio and progressive-ratio (PR) reinforcement schedules, shifted the cocaine dose-response curve downward, and inhibited intracranial BSR. Selective downregulation of astrocytic GLT-1 expression in the NAc by GLT-1 antisense oligonucleotides also inhibited cocaine self-administration. The reduction in cocaine self-administration following TFB-TBOA administration was NMDA GluN2B receptor dependent, and rats self-administering cocaine showed upregulation of GluN2B expression in NAc DA-and cAMP-regulated phosphoprotein 32 (DARPP-32)-positive medium-spiny neurons (MSNs). In contrast, TFB-TBOA, when locally administered into the NAc, VTA, or ventral pallidum (VP), dose-dependently reinstated cocaine-seeking behavior. Intra-NAc TFB-TBOA-evoked drug-seeking was long-lasting and NMDA/AMPA receptor dependent. These findings, for the first time, indicate that glutamate in the NAc negatively regulates cocaine's rewarding effects, while an excess of glutamate in multiple brain regions can trigger reinstatement of drug-seeking behavior.

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Section: Discussionmentioning

confidence: 99%

Elevation of Extracellular Glutamate by Blockade of Astrocyte Glutamate Transporters Inhibits Cocaine Reinforcement in Rats via a NMDA-GluN2B Receptor Mechanism

Yang

Hempel

et al. 2022

J. Neurosci.

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“…Therapy which was too narrow included "inadequate" cover for water-immersed wounds, the use of only anti-staphylococcal penicillins for cat and dog bites and the use of ceftriaxone monotherapy (which has limited anti-staphylococcal activity) (Zelenitsky et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Animal bite wounds and their management in tropical Australia

Vardanega

Smith

et al. 2022

International Journal of Infectious Diseases

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“…Studies investigating pharmacokinetics/pharmacodynamics of ceftriaxone in critically ill patients have suggested that there is substantial risk of failure to maintain adequate antibiotic concentrations against S. aureus in all patients with standard ceftriaxone dosing of 2 g once daily. 2 , 4 Therefore, EUCAST recommends a dosage of 2 g twice daily for S. aureus infections. 17 In our study, the majority of patients in the ceftriaxone group received 2 g once daily and no difference in bacteraemia duration was observed in comparison with flucloxacillin.…”

Section: Discussionmentioning

confidence: 99%

“…Based on pharmacokinetic/pharmacodynamic analyses and one clinical study, there are concerns that, in contrast to cefuroxime therapy, standard once-daily dosing of ceftriaxone does not lead to adequate antibiotic exposure in SAB and therefore results in suboptimal patient outcomes. 2–4 Cefuroxime and ceftriaxone have never been directly compared as empirical treatment of MSSA bacteraemia. Therefore, in this study we aimed to determine the effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with subsequent microbiologically proven MSSA bacteraemia.…”

Section: Introductionmentioning

confidence: 99%

Comparative effectiveness of β-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study

Buis

Vaart

Prins

et al. 2023

Journal of Antimicrobial Chemotherapy

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Objectives Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia Methods We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses. Results In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2–3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0–3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73–1.60 and HR 1.22, 95% CI 0.88–1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42–4.52 and sHR 1.93, 95% CI 0.67–5.60]. Conclusions In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.

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Limitations of ceftriaxone compared with cefazolin against MSSA: an integrated pharmacodynamic analysis

Cited by 18 publications

References 27 publications

Elevation of Extracellular Glutamate by Blockade of Astrocyte Glutamate Transporters Inhibits Cocaine Reinforcement in Rats via a NMDA-GluN2B Receptor Mechanism

Elevation of Extracellular Glutamate by Blockade of Astrocyte Glutamate Transporters Inhibits Cocaine Reinforcement in Rats via a NMDA-GluN2B Receptor Mechanism

Animal bite wounds and their management in tropical Australia

Comparative effectiveness of β-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study

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