Melendez R. I., Hicks M. P., Cagle S. S., Kalivas P. W. (2005). Pottabathini R., Kumar A., Bhatnagar A., Garg S., Ekavali E. (2016). Tong S.Y., Davis J.S., Eichenberger E., Holland T.L., Fowler V.G., Jr. Holland T.L., Arnold C., Fowler V.G., Jr. Clinical management of. [10] (ceftriaxone vs. SOC: 12.1% vs. 5.3%), and Barber et al. Since ceftriaxone exerts its pharmacodynamic action on bacteria by protein unbound form, concerns exist due to the high protein binding of ceftriaxone (8595%) that may result in treatment failure [6,32]. Importantly, CEF treatment (200 mg/kg/day) for 5 days decreased nicotine-seeking behavior, and this effect was associated with upregulation of GLT-1 expression in the NAc and PFC (Sari et al., 2016). In addition, CEF normalized withdrawal-induced increase in reactive species (Agostini et al., 2020) as well as the hyperactivity of lateral habenula neurons in slices from withdrawn rats (Kang et al., 2018). There was also heterogeneity in the included studies due to different sources of MSSA BSIs. In addition, CEF was suggested to bind to these mediators directly to reduce their activities (Brooks et al., 2001, 2003). Berger U. V., DeSilva T. M., Chen W., Rosenberg P. A. QUESTION 1 Joan is a 39 y/o female who presents to the clinic with a chief complaint of: 3-day history of fever (101 F degrees), chills, n & v, and flank pain. ceftriaxone decreases effects of BCG vaccine live by pharmacodynamic antagonism. Patel U.C., McKissic E.L., Kasper D., Lentino J.R., Pachucki C.T., Lee T., Lopansri B.K. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. The Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia. In addition to GLT-1, studies from Saris laboratory found that CEF also upregulated Equilibrative Nucleoside Transporter Type 1 (ENT1) in mesocorticolimbic brain regions (Sari et al., 2013b). Winans S.A., Luce A.M., Hasbun R. Outpatient parenteral antimicrobial therapy for the treatment of methicillin-susceptible Staphylococcus aureus: A comparison of cefazolin and ceftriaxone. Ceftriaxone 500 mg IM as a single dose for persons weighing <150 kg (300 lb) For persons weighing 150 kg (300 lb), 1 g of IM ceftriaxone should be administered. Similarly, earl yCEF treatment (from the day of immunization) improved the motor outcome significantly better than late administration (from the onset of motor manifestations) of an MOG peptide immunization mouse model of MS (Melzer et al., 2008). 1. T.A.A. For example, CEF (200 mg/kg/day) for 14 days improved the cognitive function and memory of a PD rat model (Ho et al., 2014). The .gov means its official. concluded that ceftriaxone at the routinely used doses may not be a reliable choice, and alternative antibiotics should be used for MSSA infections [33]. Importantly, high synaptic glutamate concentrations can lead to excitotoxicity, and it is essential to keep glutamate concentration below the toxic level by modulating EAATs (Liang et al., 2008). Neurodegeneration mediated by glutamate and beta-amyloid peptide: a comparison and possible interaction. Specifically, the treatment distribution for patients with infective endocarditis is as follows: Hamad et al. Together, there is a rich body of literature showing that repeated CEF administration for 5-7 days several weeks after initiating ethanol drinking decreased ethanol drinking and prevented a relapse-like behavior. Bacteria; Evaluation of Medication Effectiveness; University of Bridgeport NURS 206. In the United States (U.S.), S. aureus accounts for 23% of bloodstream infections (BSIs) [1,5]. Ceftriaxone is used for the treatment of congenital gonococcal conjunctivitis, A but is not licensed for this indication. Kang S., Li J., Bekker A., Ye J. H. (2018). Seib T. M., Patel S. A., Bridges R. J. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. This glutamate/glutamine/GABA cycle in glutamatergic or GABAergic systems has been found to be dysregulated in preclinical models (Rappeneau et al., 2016) and humans with neurological disorders (El-Ansary and Al-Ayadhi, 2014; Ford et al., 2017). Aal-Aaboda M., Alhaddad H., Osowik F., Nauli S. M., Sari Y. Moran M. M., McFarland K., Melendez R. I., Kalivas P. W., Seamans J. K. (2005). included six studies assessing ceftriaxone use for MSSA infections (only 1 study [22] evaluated MSSA BSIs), and they concluded that ceftriaxone was effective against MSSA infections [11]. Albrecht P., Lewerenz J., Dittmer S., Noack R., Maher P., Methner A. (2020) showed an activity-dependent increase in extracellular glutamate accumulation in the HD hippocampus that was not associated with reduced GLT-1 expression and was not reduced by ceftriaxone administration. Alcohol and cocaine exposure modulates ABCB1 and ABCG2 transporters in male alcohol-preferring rats. Additional studies are required for further elucidation of the role of ceftriaxone in the treatment of pelvic inflammatory disease and syphilis. Desce J., Godeheu G., Galli T., Artaud F., Cheramy A., Glowinski J. Benzylpenicillin differentially conjugates to IFN, TNF, IL-1, IL-4 and IL-13 but selectively reduces IFN activity. Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. Effects of ceftriaxone on chronic ethanol consumption: a potential role for xCT and GLT1 modulation of glutamate levels in male P rats. Localization of neuronal and glial glutamate transporters. Goodrich G. S., Kabakov A. Y., Hameed M. Q., Dhamne S. C., Rosenberg P. A., Rotenberg A. Ampicillin, a lactam antibiotic (200 mg/kg/day), treatment attenuated reinstatement to CP 55,940 by upregulation of GLT-1 (Hakami et al., 2018). official website and that any information you provide is encrypted Received 2022 Feb 9; Accepted 2022 Mar 8. An official website of the United States government. Montana V., Verkhratsky A., Parpura V. (2014). Moreover, CEF increases BDNF and TrkB expression (Thne-Reineke et al., 2008). Furthermore, human P-gp was significantly inhibited in a concentration-dependent manner by buprenorphine, methadone, and THC (Tournier et al., 2010). Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Sex Transm Dis. CSF glutamate levels are significantly increased in patients with Alzheimers disease compared to healthy controls in some (Pomara et al., 1992; Csernansky et al., 1996) but not all studies (Martinez et al., 1993; Kuiper et al., 2000), and a 3xTg-AD mouse model shows age-dependent progressive reduction in hippocampal GLT-1 levels (Zumkehr et al., 2015). ATP-sensitive potassium channels functioning as neuronal metabolic sensors in diabetes mellitus. It has been found that pre-treatment with CEF (200 mg/kg IP) for 5 days reduced the ischemia-increased mRNA expression of pro-inflammatory cytokines including Fas, FasL,IL-6, and TNF- (Chu et al., 2007). 1Division of Infectious Diseases, Alpert Medical School, Brown University, Providence, RI 02903, USA; ude.nworb@hedahehs_idaf, 2Division of Infectious Diseases, Rhode Island Hospital, Providence, RI 02903, USA; gro.napsefil@zetinebg, 3Department of Clinical Pharmacy, College of Pharmacy, Hail University, P.O. Onetti C. G., Marquez-Gamio S., Vera-Delgado K. S., Obregn-Herrera A. Staphylococcus aureus is one of the most common pathogenic Gram-positive bacteria, and it causes a wide range of community-acquired and hospital-acquired infections [1,2]. As such, higher brain CEF concentration is expected in animal models of dependence during the drug administration phase compared to the withdrawal or the abstinence phase. independently screened the titles and abstracts of all the identified studies in the databases for eligibility. In addition to attenuation of visceral pain, it has been found that CEF upregulated GLT-1 expression in the spinal cord (Ackerman et al., 2016). Thus, ceftriaxone is convenient to use, especially in outpatient parenteral antimicrobial therapy (OPAT) settings without hospitalization [7]. Furthermore, CEF injection at 200 mg/kg/day (IP) for 5-7 days increased GLT-1 expression and glutamate uptake in an animal model of Parkinsons disease, and this effect was observed for 4 and 7-14 days, respectively, after treatments in nave rats (Chotibut et al., 2014). In addition to Ca2+, glutamate can also affect other signaling pathways such as Na+ and K+ channels, which might be involved in the pathogenesis of neuropsychiatric disorders including schizophrenia, seizure, and acute ischemia (Lysko et al., 1994; Farber et al., 2002; Wang et al., 2004; Inyushin et al., 2010). Conditional deletion of the glutamate transporter GLT-1 reveals that astrocytic GLT-1 protects against fatal epilepsy while neuronal GLT-1 contributes significantly to glutamate uptake into synaptosomes. However, it prevented cocaine preference in the CPP paradigm. Stimulus-evoked field extracellular postsynaptic potentials recorded in the CA1 region of the hippocampus of conditional GLT-1 knockout (KO) mouse lines were normal in the astrocytic GLT-1 KO with elevated glutamate and were reduced in the neuronal GLT-1 KO but with normal glutamate accumulation. A plausible explanation is that patients with infective endocarditis as a source of BSI have high bacterial inoculum and should be treated based on the SOC for infective endocarditis [34]. Alshehri F. S., Hakami A. Y., Althobaiti Y. S., Sari Y. Based on the argument that hyperglutamatergic state contributes to the development of several neurological and psychiatric diseases, decrease in GLT-1 and xCT expression can lead to hyperglutamatergic state, and upregulating these transporters by the -lactam antibiotic CEF, known to upregulate GLT-1 and xCT, could be a potential pharmacological approach to attenuate glutamate dysregulation (Rothstein et al., 2005; Sari et al., 2011; Das et al., 2015). beta-Lactam antibiotic inhibits development of morphine physical dependence in rats. A., Camsari U. M., Ruby C. L., Kasasbeh A., Choi S., Choi D. S. (2014). Problems in the treatment of bacterial sexually transmitted diseases. (2021). PMCID: PMC183664 DOI: 10.1128/AAC.22.1.1 Abstract The in vitro activity of ceftriaxone against 437 clinical isolates of gram-negative bacilli was determined. (2009). Ceftriaxone rescues hippocampal neurons from excitotoxicity and enhances memory retrieval in chronic hypobaric hypoxia. We resolved discrepancies through discussion and consensus; unresolved matters were reviewed by a third person (F.S.). Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Decreased expression of GLT-1 in the R6/2 model of Huntingtons disease does not worsen disease progression. It was found that the GLT-1 in astrocytes plays a role in neuroprotection against neuro-excitotoxicity, and that neuronal GLT-1 is essential for glutamate uptake (Danbolt, 2001; Petr et al., 2015). The rate of infection recurrence was not statistically different between ceftriaxone and SOC: Carr et al. Available online: Borenstein M., Hedges L.V., Higgins J.P., Rothstein H.R. In addition, we manually searched the citations of key studies. Studies have found that mTOR is involved in the psychiatric disorder-induced hyperglutamatergic state such as certain types of depression (Crino, 2016). A similar argument has been made by Kong et al. NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala. A recent systematic review and meta-analysis and another systematic review evaluated ceftriaxone use for MSSA infections [11,12]. Snchez-Blzquez P., Rodrguez-Muoz M., Garzn J. Macaluso A., Bernabucci M., Trabucco A., Ciolli L., Troisi F., Baldini R., et al. (2005). We executed the search with the following concepts: ceftriaxone, BSI, and MSSA. Increase in glutamate efflux from pre-synaptic neurons (Nishizawa, 2001) and reversal of GLT-1 (Roettger and Lipton, 1996; Seki et al., 1999) caused excitotoxicity in an ischemic stroke model. For instance, nicotine exposure increased extracellular glutamate concentrations by stimulation of nicotinic acetylcholine receptors (nAChRs) (Konradsson-Geuken et al., 2009). Fujio M., Nakagawa T., Sekiya Y., Ozawa T., Suzuki Y., Minami M., et al. Egger M., Davey Smith G., Schneider M., Minder C. Bias in meta-analysis detected by a simple, graphical test. Ceftriaxone injection is used to treat certain infections caused by bacteria such as gonorrhea (a sexually transmitted disease), pelvic inflammatory disease (infection of the female reproductive organs that may cause infertility), meningitis (infection of the membranes that surround the brain and spinal cord), and infections of the lungs, ears, . Glt1 modulation of glutamate levels in male P rats certain types of depression ( Crino, )... 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