Ceftriaxone Treatment Research Articles

Ceftriaxone and MC-100093 mitigate fentanyl-induced cardiac injury in mice: Preclinical investigation of its underlying molecular mechanisms

Drug addiction is considered a worldwide concern and one of the most prevailing causes of death globally. Opioids are highly addictive drugs, and one of the most common opioids that is frequently used clinically is fentanyl. The potential harmful effects of chronic exposure to opioids on the heart are still to be elucidated. Although β-lactam antibiotics are well recognized for their ability to fight bacteria, its protective effect in the brain and liver has been reported. In this study, we hypothesize that β-lactam antibiotic, ceftriaxone, and the novel synthetic non-antibiotic β-lactam, MC-100093, are cardioprotective against fentanyl induced-cardiac injury by upregulating xCT expression. Mice were exposed to repeated low dose (0.05 mg/kg, i.p.) of fentanyl for one week and then challenged on day 9 with higher dose of fentanyl (1 mg/kg, i.p.). This study investigated cardiac histopathology and target genes and proteins in serum and cardiac tissues in mice exposed to fentanyl overdose and β-lactams. We revealed that fentanyl treatment induced cardiac damage as evidenced by elevated cardiac enzymes (troponin I). Furthermore, fentanyl treatment caused large aggregations of inflammatory cells and elevation in the areas and volumes of myocardial fibers, indicating hypertrophy and severe cardiac damage. Ceftriaxone and MC-100093 treatment, However, induced cardioprotective effects as evidenced by marked reduction in cardiac enzymes (troponin I) and changes in histopathology. Furthermore, ceftriaxone and MC-100093 treatment decreased the levels of hypertrophic genes (α-MHC & β-MHC), apoptotic (caspase-3), and inflammatory markers (IL-6 & NF-κB). This study reports for the first time the cardioprotective effect of β-lactams against fentanyl-induced cardiac injury. Further studies are greatly encouraged to completely identify the cardioprotective properties of ceftriaxone and MC-100093.

Clinical outcomes in patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection.

A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates. We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic. We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90 day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups. Sixty-two patients were included in our analysis. Overall, median age was 63 years (IQR 49.5-71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0 days (IQR 9.0-16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30-1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%. These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone.

Heparin-Binding Protein Promotes Acute Lung Injury in Sepsis Mice by Blocking the Aryl Hydrocarbon Receptor Signaling Pathway.

This study aimed to explore the therapeutic effect and potential mechanism of heparin-binding protein (HBP) reduction on sepsis-related acute lung injury. We utilized a murine model of sepsis-induced by intraperitoneal injection of lipopolysaccharides (LPS) in C57BL/6J mice divided into four groups: Control, LPS, Anti-HBP, and ceftriaxone (CEF). Following sepsis induction, Anti-HBP or CEF treatments were administered, and survival rates were monitored for 48 h. We then used reverse-transcription quantitative PCR to analyze the expression levels of HBP in lung tissues, immunohistochemistry for protein localization, and Western blotting for protein quantification. Pulmonary inflammation was assessed using enzyme-linked immunosorbent assays of proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, and interferon-γ). The activation state of the aryl hydrocarbon receptor (AhR) signaling pathway was determined via Western blotting, evaluating both cytoplasmic and nuclear localization of AhR and the expression of cytochrome P450 1A1 protein by its target gene. Anti-HBP specifically reduced HBP levels. The survival rate of mice in the Anti-HBP and CEF groups was much higher than that in the LPS group. The severity of lung injury and pulmonary inflammatory response in the Anti-HBP and CEF groups was significantly lower than that in the LPS group. AhR signaling pathway activation was observed in the Anti-HBP and CEF groups. Additionally, there was no significant difference in the above indices between the Anti-HBP and CEF groups. HBP downregulation in lung tissues significantly improved LPS-induced lung injury and the pulmonary inflammatory response, thereby prolonging the survival of sepsis mice, suggesting activation of the AhR signaling pathway. Moreover, the effect of lowering the HBP level was equivalent to that of the classical antibiotic CEF. Not applicable.

Effects of Hydrocodone Overdose and Ceftriaxone on Astrocytic Glutamate Transporters and Glutamate Receptors, and Associated Signaling in Nucleus Accumbens as well as Locomotor Activity in C57/BL Mice.

Chronic opioid treatments dysregulate the glutamatergic system, inducing a hyperglutamatergic state in mesocorticolimbic brain regions. This study investigated the effects of exposure to hydrocodone overdose on locomotor activity, expression of target proteins related to the glutamatergic system, signaling kinases, and neuroinflammatory factors in the nucleus accumbens. The locomotor activity of mice was measured using the Comprehensive Laboratory Animal Monitoring System (CLAMS). CLAMS data showed that exposure to hydrocodone overdose increased locomotion activity in mice. This study tested ceftriaxone, known to upregulate major glutamate transporter 1 (GLT-1), in mice exposed to an overdose of hydrocodone. Thus, ceftriaxone normalized hydrocodone-induced hyperlocomotion activity in mice. Furthermore, exposure to hydrocodone overdose downregulated GLT-1, cystine/glutamate antiporter (xCT), and extracellular signal-regulated kinase activity (p-ERK/ERK) expression in the nucleus accumbens. However, exposure to an overdose of hydrocodone increased metabotropic glutamate receptor 5 (mGluR5), neuronal nitric oxide synthase activity (p-nNOS/nNOS), and receptor for advanced glycation end products (RAGE) expression in the nucleus accumbens. Importantly, ceftriaxone treatment attenuated hydrocodone-induced upregulation of mGluR5, p-nNOS/nNOS, and RAGE, as well as hydrocodone-induced downregulation of GLT-1, xCT, and p-ERK/ERK expression. These data demonstrated that exposure to hydrocodone overdose can cause dysregulation of the glutamatergic system, neuroinflammation, hyperlocomotion activity, and the potential therapeutic role of ceftriaxone in attenuating these effects.

A case of pediatric enteroviral meningitis with a travel history

Enterovirus meningitis represents a common cause of meningitis worldwide. In this case study, a 5-year-old male with a travel history presenting with persistent nausea, vomiting, fever and headache for 3 days is reported. The patient described a fever of 39.5°C on the first day of symptom onset as well as decreased appetite and pain in the front right side of head. In physical examination, initially there was no sign of stiff neck, however he had neck stiffness the following day, Kernig's sign and Brudzinski's signs were positive. On admission, blood tests showed a slightly increased C-reactive protein and a normal white cell count. He was admitted to the pediatrics service and a lumbar puncture was performed. Intravenous ceftriaxone and acyclovir were empirically administered. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, with normal protein and glucose concentration. CSF molecular analysis was positive for enterovirus RNA. Cranial magnetic resonance imaging with contrast was normal. Following confirmed diagnosis, ceftriaxone and acyclovir treatments were discontinued and he was given supportive care. He successfully recovered and was discharged without any complication. This case report highlights that rapid molecular testing favorably impacts patient management by improving antimicrobial stewardship through the reduction of intravenous therapy, side effects and inpatient bed-days.

Pharmacodynamic evaluation of ceftriaxone single-dose therapy (0.125-1 g) to eradicate ceftriaxone-susceptible and ceftriaxone-resistant Neisseria gonorrhoeae strains in a hollow fibre infection model for gonorrhoea.

Antimicrobial resistance in Neisseria gonorrhoeae is threatening the gonorrhoea treatment, and optimizations of the current ceftriaxone-treatment regimens are crucial. We evaluated the pharmacodynamics of ceftriaxone single-dose therapy (0.125-1 g) against ceftriaxone-susceptible and ceftriaxone-resistant gonococcal strains, based on EUCAST ceftriaxone-resistance breakpoint (MIC > 0.125 mg/L), in our hollow fibre infection model (HFIM) for gonorrhoea. Gonococcal strains examined were WHO F (ceftriaxone-susceptible, MIC < 0.002 mg/L), R (ceftriaxone-resistant, MIC = 0.5 mg/L), Z (ceftriaxone-resistant, MIC = 0.5 mg/L) and X (ceftriaxone-resistant, MIC = 2 mg/L). Dose-range HFIM 7 day experiments simulating ceftriaxone 0.125-1 g single-dose intramuscular regimens were conducted. Ceftriaxone 0.125-1 g single-dose treatments rapidly eradicated WHO F (wild-type ceftriaxone MIC). Ceftriaxone 0.5 and 1 g treatments, based on ceftriaxone human plasma pharmacokinetic parameters, eradicated most ceftriaxone-resistant gonococcal strains (WHO R and Z), but ceftriaxone 0.5 g failed to eradicate WHO X (high-level ceftriaxone resistance). When simulating oropharyngeal gonorrhoea, ceftriaxone 0.5 g failed to eradicate all the ceftriaxone-resistant strains, while ceftriaxone 1 g eradicated WHO R and Z (low-level ceftriaxone resistance) but failed to eradicate WHO X (high-level ceftriaxone resistance). No ceftriaxone-resistant mutants were selected using any ceftriaxone treatments. Ceftriaxone 1 g single-dose intramuscularly cure most of the anogenital and oropharyngeal gonorrhoea cases caused by the currently internationally spreading ceftriaxone-resistant gonococcal strains, which should be further confirmed clinically. A ceftriaxone 1 g dose (±azithromycin 2 g) should be recommended for first-line empiric gonorrhoea treatment. This will buy countries some time until novel antimicrobials are licensed. Using ceftriaxone 1 g gonorrhoea treatment, the EUCAST ceftriaxone-resistance breakpoint is too low.

Penı̇sı̇lı̇n ile Oluşturulan Deneysel Epilepsi Modelinde Seftrı̇aksonun Etkı̇sı̇: Elektrofı̇zyolojı̇k Bı̇r Çalışma

Introduction: Epilepsy is a set of chronic neurological disorders characterized by seizures associated with abnormal and uncontrolled neuronal activity of the brain. Glutamate is the main excitatory neurotransmitter in the central nervous system. Excitatory amino acid transporter-2 (EAAT2), one of the major glutamate transporters, is responsible for total glutamate intake. Ceftriaxone is a β-lactam antibiotic that increases EAAT-2 expression and functional activity. This study aims to investigate the effects of ceftriaxone on penicillin-induced epileptiform activity by using electrocorticography (ECoG) in anesthetized rats.&#x0D; Materials and Methods: In this study, 35 Wistar male rats were used. The rats were divided into five groups of 7. In group 1, 2.5 μL 500 IU of penicillin intracranially (i.c.) and 1 ml saline solution and intraperitoneally (i.p.) were given, respectively. In group 2, 200 mg/kg, i.p. of ceftriaxone was administered 30 minutes after penicillin. In group 3, 400 mg/kg of ceftriaxone was administered i.p. 30 minutes after penicillin. 500 mg/kg of sodium valproate was administered i.p. following 30 minutes of penicillin in group 4. In group 5, 400 mg/kg, i.p. of ceftriaxone and 500 mg/kg, i.p. of sodium valproate were administered 30 minutes after penicillin. The rats were placed in a stereotaxic device after the procedure, and electrocorticogram recordings were captured for 180 minutes.&#x0D; Results: The acute treatment of ceftriaxone reduced spike-wave frequency and spike-wave amplitude of penicillin-induced epileptiform activity in the rats. &#x0D; Conclusion: These findings suggest that acute ceftriaxone had an anticonvulsant effect on penicillin-induced focal onset epileptic activity. Ceftriaxone may has an anti-epileptogenic potential.

Ceftriaxone alters the gut microbiome composition and reduces alcohol intake in male and female Sprague–Dawley rats

Ceftriaxone is an antibiotic that increases central nervous system (CNS) protein expression of the glutamate transporters GLT-1 and xCT and ameliorates pathological behaviors in rodent models of neurological disease and substance use disorder. However, little ceftriaxone passes through the blood–brain barrier, the CNS binding partner of ceftriaxone is unknown, and ceftriaxone does not consistently upregulate GLT-1 and xCT in cell culture. Ceftriaxone alters the gut microbiome composition in rodents and humans, and the microbiome–gut–brain axis regulates drug-seeking. Thus, here we test the hypothesis that ceftriaxone reduces alcohol intake while ameliorating alcohol-induced disruption of the gut microbiome composition. Male and female Sprague–Dawley rats received intermittent access to alcohol (IAA) while controls received access to only water. Following 17 IAA sessions, ceftriaxone/vehicle treatment was given for 5 days. Analysis of the gut microbiome composition was assessed by 16S rRNA gene amplicon sequencing conducted on fecal pellets collected prior to and after alcohol consumption and following ceftriaxone treatment. Male rats displayed escalated alcohol intake and preference over the course of the 17 sessions; however, total alcohol intake did not differ between the sexes. Ceftriaxone reduced alcohol intake and preference in male and female rats. While alcohol affected a diverse set of amplicon sequencing variants (ASV), ceftriaxone markedly reduced the diversity of microbial communities reflected by a blooming of the Enterococcaceae family. The remaining effects of ceftriaxone, however, encompassed families both affected and unaffected by prior alcohol drinking and highlight the Ruminococcaceae and Muribaculaceae families as bidirectionally modulated by alcohol and ceftriaxone. Altogether, our study confirms that ceftriaxone reduces alcohol intake in rats and partially reverses alcohol-induced dysbiosis.

198 Impact of pregnancy on ceftriaxone pharmacokinetics and treatment of syphilis: physiologic-based population PK modeling approach

198 Impact of pregnancy on ceftriaxone pharmacokinetics and treatment of syphilis: physiologic-based population PK modeling approach

2776. Decrease in ceftriaxone treatment failure rates for infections caused by inducible AmpC producing Enterobacterales associated with changes in laboratory susceptibility testing reporting

Abstract Background Due to the risk of AmpC induction and subsequent emergence of resistance on therapy, IDSA guidelines suggest avoiding ceftriaxone (CRO) for the treatment of E. cloacae, K. aerogenes or C. freundii (CEK group) but not for S. marcescens (SM), citing the lack of evidence. Many clinical laboratories still report CRO susceptibilities for these organisms. In January 2021, our institution stopped reporting CRO results for Enterobacterales with inducible AmpC enzymes. We compare rates of CRO treatment failure in the 2 years before and after this reporting change. Methods We retrospectively evaluated (with IRB approval) all hospitalized patients that were diagnosed with an invasive infection due to CRO-susceptible Serratia, Enterobacter, K. aerogenes, or C. freundii. Final therapy was defined as antibiotic the patient was on within 24h of culture finalization for at least a 72h course. The primary outcome assessed rates of CRO treatment failure- defined as clinical failure (clinical decompensation) or microbiological failure (repeat growth of same organism). The years 2019 and 2020 (lab reported CRO) were compared to 2021 and 2022 (lab did not report CRO). Results In 2019-2020, 67 patients were hospitalized with bacteremia, endocarditis, pneumonia or urosepsis (25 by SM, 42 by CEK group). 15 (22.4%) were treated with CRO (6 SM, 9 CEK). 12 patients (80%) failed CRO therapy (5 SM, 7 CEK), of which 4 had a repeat organism cultured, with 1 documented CRO-resistant isolate (E. cloacae) after treatment. In 2021-2022, of the 77 patients with infections (34 by SM, 43 by CEK group), 2 (2.6%) were treated with CRO and both failed therapy (2 SM).Table 1.Summary of results. * CRO treatment failure rates based on number of patients who showed clinical or microbiology failure after being placed on CRO treatment Conclusion Our single-center evaluation suggests that laboratories not reporting CRO susceptibility results for Enterobacterales with inducible AmpC may decrease use of CRO for these organisms and decrease subsequent treatment failures. Larger multi-center studies are warranted. Contrary to the IDSA guidelines, SM infections had a similar risk of CRO treatment failure as infections by CEK organisms, despite the initial isolate’s susceptibility. We hypothesize that due to the complex mechanism of inducible AmpC resistance, most cases of CRO treatment failure are not accompanied with the repeat culturing of a CRO-resistant organism after therapy. Disclosures Romney Humphries, PhD, D(ABMM), M(ASCP), Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Ventorx: Advisor/Consultant

Ceftriaxone and the Risk of Ventricular Arrhythmia, Cardiac Arrest, and Death Among Patients Receiving Lansoprazole

The combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates to clinically important patient outcomes. To compare lansoprazole with another proton pump inhibitor (PPI) during ceftriaxone treatment in terms of risk for ventricular arrhythmia, cardiac arrest, and in-hospital mortality. A retrospective cohort study including adult medical inpatients receiving ceftriaxone with lansoprazole or another PPI in 13 hospitals in Ontario, Canada, was conducted from January 1, 2015, to December 31, 2021. Lansoprazole during ceftriaxone treatment vs other PPIs during ceftriaxone treatment. The primary outcome was a composite of ventricular arrhythmia or cardiac arrest that occurred after hospital admission. The secondary outcome was all-cause in-hospital mortality. Propensity-score weighting was used to adjust for covariates including hospital site, demographic characteristics, comorbidities, risk factors for ventricular arrhythmia, illness severity, admitting diagnoses, and concomitant medications. Of the 31 152 patients hospitalized on internal medicine wards who were treated with ceftriaxone while receiving a PPI, 16 135 patients (51.8%) were male, and the mean (SD) age was 71.7 (16.0) years. The study included 3747 patients in the lansoprazole group and 27 405 patients in the other PPI group. Ventricular arrhythmia or cardiac arrest occurred in 126 patients (3.4%) within the lansoprazole group and 319 patients (1.2%) within the other PPI group. In-hospital mortality occurred in 746 patients (19.9%) within the lansoprazole group and 2762 patients (10.1%) in the other PPI group. After weighting using propensity scores, the adjusted risk difference for the lansoprazole group minus other PPI group was 1.7% (95% CI, 1.1%-2.3%) for ventricular arrhythmia or cardiac arrest and 7.4% (95% CI, 6.1%-8.8%) for in-hospital mortality. The findings of this cohort study suggest that combination therapy with lansoprazole and ceftriaxone should be avoided. More studies are needed to determine whether these findings could be replicated in other populations and settings.

Effects of Chronic Hydrocodone Exposure and Ceftriaxone on the Expression of Astrocytic Glutamate Transporters in Mesocorticolimbic Brain Regions of C57/BL Mice.

Exposure to opioids can lead to the alteration of several neurotransmitters. Among these neurotransmitters, glutamate is thought to be involved in opioid dependence. Glutamate neurotransmission is mainly regulated by astrocytic glutamate transporters such as glutamate transporter 1 (GLT-1) and cystine/glutamate antiporter (xCT). Our laboratory has shown that exposure to lower doses of hydrocodone reduced the expression of xCT in the nucleus accumbens (NAc) and the hippocampus. In the present study, we investigated the effects of chronic exposure to hydrocodone, and tested ceftriaxone as a GLT-1 upregulator in mesocorticolimbic brain regions such as the NAc, the amygdala (AMY), and the dorsomedial prefrontal cortex (dmPFC). Eight-week-old male mice were divided into three groups: (1) the saline vehicle control group; (2) the hydrocodone group; and (3) the hydrocodone + ceftriaxone group. Mice were injected with hydrocodone (10 mg/kg, i.p.) or saline for 14 days. On day seven, the hydrocodone/ceftriaxone group was injected with ceftriaxone (200 mg/kg, i.p.) for last seven days. Chronic exposure to hydrocodone reduced the expression of GLT-1, xCT, protein kinase B (AKT), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal Kinase (JNK) in NAc, AMY, and dmPFC. However, hydrocodone exposure increased the expression of G-protein-coupled metabotropic glutamate receptors (mGluR5) in the NAc, AMY, and dmPFC. Importantly, ceftriaxone treatment normalized the expression of mGluR5, GLT-1, and xCT in all these brain regions, except for xCT in the AMY. Importantly, ceftriaxone treatment attenuated hydrocodone-induced downregulation of signaling pathways such as AKT, ERK, and JNK expression in the NAc, AMY, and dmPFC. These findings demonstrate that ceftriaxone has potential therapeutic effects in reversing hydrocodone-induced downregulation of GLT-1 and xCT in selected reward brain regions, and this might be mediated through the downstream kinase signaling pathways such as AKT, ERK, and JNK.

Economic evaluation of antimicrobial resistance in curable sexually transmitted infections; a systematic review and a case study.

To provide a summary of the economic and methodological evidence on capturing antimicrobial resistance (AMR) associated costs for curable sexually transmitted infections (STIs). To explore approaches for incorporating the cost of AMR within an economic model evaluating different treatment strategies for gonorrhoea, as a case study. A systematic review protocol was registered on PROSPERO (CRD42022298232). MEDLINE, EMBASE, CINAHL, Cochrane Library, International Health Technology Assessment Database, National Health Service Economic Evaluation Database, and EconLit databases were searched up to August 2022. Included studies were analysed, quality assessed and findings synthesised narratively. Additionally, an economic evaluation which incorporated AMR was undertaken using a decision tree model and primary data from a randomised clinical trial comparing gentamicin therapy with standard treatment (ceftriaxone). AMR was incorporated into the evaluation using three approaches-integrating the additional costs of treating resistant infections, conducting a threshold analysis, and accounting for the societal cost of resistance for the antibiotic consumed. Twelve studies were included in the systematic review with the majority focussed on AMR in gonorrhoea. The cost of ceftriaxone resistant gonorrhoea and the cost of ceftriaxone sparing strategies were significant and related to the direct medical costs from persistent gonorrhoea infections, sequelae of untreated infections, gonorrhoea attributable-HIV transmission and AMR testing. However, AMR definition, the collection and incorporation of AMR associated costs, and the perspectives adopted were inconsistent or limited. Using the review findings, different approaches were explored for incorporating AMR into an economic evaluation comparing gentamicin to ceftriaxone for gonorrhoea treatment. Although the initial analysis showed that ceftriaxone was the cheaper treatment, gentamicin became cost-neutral if the clinical efficacy of ceftriaxone reduced from 98% to 92%. By incorporating societal costs of antibiotic use, gentamicin became cost-neutral if the cost of ceftriaxone treatment increased from £4.60 to £8.44 per patient. Inclusion of AMR into economic evaluations may substantially influence estimates of cost-effectiveness and affect subsequent treatment recommendations for gonorrhoea and other STIs. However, robust data on the cost of AMR and a standardised approach for conducting economic evaluations for STI treatment which incorporate AMR are lacking, and requires further developmental research.

Culture-Based Identification of Causative Organisms in Ascitic Fluids of Patients with Spontaneous Bacterial Peritonitis Secondary to Decompensated Liver Disease and their Sensitivities to Ceftriaxone as an Empiric Therapy

OBJECTIVES To identify the pathogens in the ascitic fluids of patients with spontaneous bacterial peritonitis and then to determine their sensitivity pattern to ceftriaxone. METHODOLOGY The cross-sectional study was conducted at the Medical Unit-A, Department of Medicine, Hayatabad Medical Complex, Peshawar, from November 2021 to April 2022. Before ceftriaxone treatment was started, a minimum of 10 ml of ascitic fluid was introduced into a blood culture vial. Only patients with a positive culture were registered, and their information was gathered using a proforma. For statistical analysis, SPSS version 23 was used. RESULTSA total of 96 patients were enrolled in our study. There were 62 (59.52%) male and 34 (40.48%) female patients. Based on the isolation and identification of bacteria, the most prevalent bacteria isolated was Escherichia coli in 36 (37.5%) patients, followed by Acinetobacter Spp in 13 (13.54%) patients, Streptococcus spp in 14 (14.58%), Enterococcus spp in 11 (11.45%), Staphylococcus aureus in 9 (9.39%), MRSA in 8(8.33%) and K. Pneumonia in 5(5.21%) patients. The overall sensitivity of ceftriaxone to gram-positive bacteria was observed in 12 (42.85%) isolates, whereas the overall sensitivity of ceftriaxone to gram-negative bacteria was observed in 25 (36.76%) isolates. (p=0.091) (Figure 6). CONCLUSION Our study concludes that gram-negative bacteria were more prevalent than gram-positive bacteria in ascitic fluids of patients with spontaneous bacterial peritonitis. The most common isolated pathogen was E.coli. Gram-negative was more resistant to ceftriaxone as compared to gram-positive bacteria.

Evaluation of Blood Pressure in Children Treated with Ceftriaxone: A Case-Control Study

Background: In children, high blood pressure can develop into hypertension and its consequences during puberty and adulthood. High blood pressure in children is often secondary to other causes, including renal diseases. Nephrolithiasis is one of the causes of secondary hypertension. The extensive use of cephalosporins in hospitals, particularly ceftriaxone, can result in nephrolithiasis. Therefore, the purpose of this study was to assess the relationship between ceftriaxone treatment and elevated blood pressure in children. Method: The research was conducted as a case-control study over an 18-month period from 2018 to 2019. In this study, blood pressure was measured in 111 children aged 3-13 years who were hospitalized at Amir Kabir Hospital in Arak and received ceftriaxone for at least 48 hours. As a control group, 111 children who did not receive ceftriaxone had their blood pressure measured. The blood pressure levels and percentiles of children in the two groups were then compared. Result: In the case and control groups, the mean age was 5.1±1.61 and 6.04±2.4 years, and the mean height was 109.17±10.71 and 114.86±12.95 cm, respectively. A slightly higher mean systolic blood pressure percentile was observed in the case group (65.59±18.17) than in the control group (65.28±14.51) (P=0.112), and the mean diastolic blood pressure percentile was also slightly higher in the case group (58.89±18.88) than in the control group (54.85±19.28) (P=0.317). The difference in diastolic blood pressure was greater than in systolic blood pressure. However, these detected differences were slight and not statistically significant. Conclusion: This study showed no association between blood pressure levels and ceftriaxone treatment in children older than three years who received the medicine for at least 48 hours. However, additional research is suggested, focusing on the effects of the medicine at higher doses and over a longer period of time following administration.

Initial antimicrobial therapy and case fatality in patients with community-acquired pneumonia

The health importance of community-acquired pneumonia is an unquestionable fact given its relationship with hospital and overall mortality. The objective of the investigation was to evaluate the relationship between selected antimicrobials used in the initial treatment (amoxicillin/sulbactam, cefuroxime, ceftriaxone and cefotaxime) and mortality from pneumonia. An observational study was carried out, with a descriptive design and a population of 1,809 patients with pneumonia hospitalized between 2012 and 2019; the necessary information was obtained from the clinical history. Statistical processing was performed using bivariate and multivariate analysis (logistic regression); the ratio of cross products (odds ratio) and its 95% confidence interval were used as a statistician. Among the results, the following stand out: significantly higher lethality values were found in those treated with cefotaxime (33%) than in those who received amoxicillin/sulbactam (24%, OR 1.6[1.0001;2.6]), as well as in those treated with ceftriaxone (30%) compared with those treated with amoxicillin/sulbactam (24%, OR 1.3[1.05;1.8]) and with cefuroxime (24%, OR 1.3[1.04;1.7]). A higher frequency of patients with extensive pneumonia, of patients in a critical state on admission, and of bedridden occurrence during hospitalization were identified in those treated with cefotaxime. In patients with “moderate pneumonia and high probability of unfavorable outcome”, treatment with ceftriaxone or cefotaxime was associated with death; as well as ceftriaxone treatment for all subjects. It is concluded that the initial treatment with amoxicillin/ sulbactam or cefuroxime was more favorable than the use of third generation cephalosporins. Also in the global analysis, the absence of differences in lethality between those treated with amoxicillin/sulbactam and with cefuroxime was recognized.

Repairing effects of Lactobacillus acidophilus on ceftriaxone-induced intestinal dysbacteriosis in mice

To investigate the repairing effect of Lactobacillus acidophilus LA11-Only on ceftriaxone induced intestinal micronbiota imbalance in mice and its alleviating effect on lipid metabolism. A total of 30 SPF BALB/c male mice were randomly divided into control group(10) and model group(20). The model group was given ceftriaxone sodium solution by gavage for a week to create a mouse model of antibiotic flora disorder. The natural recovery group(10) was given 10% skimmed milk solution by gavage, and the LA11-Onlly group was given Lactobacillus acidophilus skimmed milk solution(1.0×10~9CFU/mL). Two weeks later, the feces were collected aseptically.16S rRNA sequencing technology and ultra-high-performance liquid chromatography combined with mass spectrometry(UPLC-MS) were used to analyze the repair effect of LA11-Onlly on antibiotic induced bacterial flora disorder and lipid metabolism in mice. After ceftriaxone treatment, the diversity of intestinal microbiota in mice decreased, and there was a significant difference in the composition of flora compared with the control group; After treatment with LA11-Onlly, the Alpha diversity increased, the abundance of beneficial bacteria such as Lactobacillus and Butyricicoccus increased, and the composition of flora was closer to the control group; At the same time, the concentration of short chain fatty acids(SCFAs) increased in varying degrees. Compared with the natural recovery group, the levels of butyric acid and valeric acid in LA11-Onlly group increased significantly, close to the same level as the control group. Lactobacillus acidophilus LA11-Onlly probiotics can inhibit the growth of harmful bacteria by regulating the diversity and community composition of intestinal microbiota, promote the increase of the concentration of SCFAs, and alleviate the damage of antibiotics to the body.

Outbreak of Gastrointestinal Infections Caused by Yersinia enterocolitica in Children, Medellín, Colombia

Abstract Objective In this study, we describe the clinical and epidemiological characteristics of a cluster of children with acute gastrointestinal (GI) infection caused by Yersinia enterocolitica in Medellín, Colombia. Methods A retrospective descriptive observational study was performed with the information recorded in clinical charts of GI infection cases caused by Y. enterocolitica in pediatric population of two hospital institutions in Medellín, Colombia. The microorganism identification was performed directly from stool samples using molecular biology techniques and from stool cultures using mass spectrometry. Space-time simulations and antibiotic susceptibility profiles were performed using Whonet 5.6 and Clinical and Laboratory Standards Institute 2020 guide. Results A total of 37 cases were identified in children younger than 15 years; between November 2020 and January 2021, 45.9% of cases were in children aged 1 to 5 years. Most children had diarrhea (97.3%) and fever (67.6%), 21.6% had abdominal pain and vomiting, and 13.5% had hyporexia. Sixteen of the patients (43.2%) received azithromycin, 24.3% (n = 9) received ceftriaxone, and 13.5% (n = 5) received a combined treatment of ceftriaxone and azithromycin or azithromycin and metronidazole. Based on space-time simulations, the clonality analysis and the characteristics of the cases suggest a community outbreak of unknown origin. Conclusion Our findings confirm the occurrence of an outbreak related to Y. enterocolitica from the community whose source could not be identified. Although it is presumed that the frequency of this microorganism is low in these regions, the use of new diagnostic tools in clinical microbiology allowed the early identification of the epidemiological event.

Evaluation of ceftriaxone pharmacokinetics in hospitalized Egyptian pediatric patients

This study aimed to evaluate ceftriaxone pharmacokinetics that affects the achievement of targets in the treatment of critically ill children (meningitis, pneumonia, urinary tract infection, peritonitis, and infective endocarditis( who were admitted to Zagazig University Pediatric hospital in Egypt to monitor for the drug adverse effects.Blood samples were obtained from 24 hospitalized pediatric patients (ages ranging from 2.5 months to 12 years) after administering the calculated dose of ceftriaxone via intravenous bolus route. Then, ceftriaxone plasma concentrations were measured using a validated HPLC method with ultraviolet detection. The pharmacokinetic analysis was conducted using Phoenix Winnonlin Program® software.Data for total and free ceftriaxone best fitted on a one-compartment model with the first-order elimination process. Clearance of ceftriaxone is reduced for patients with reduced kidney function and increased with those with augmented renal clearance. The volume of distribution and the free fraction are increased in these patients, especially those with hypoalbuminemia with a shorter half-life time were detected. A slight increase in total bilirubin and liver enzymes has been observed after treatment with ceftriaxone in these patients. Conclusion: In most critically ill pediatric patients, the current ceftriaxone treatment regimen (50 to 100 mg/kg) offers adequate pathogenic coverage. The clearance of free ceftriaxone in all patients correlates well with their renal function (eGFR), with r2 = 0.7252. During therapy with ceftriaxone at all doses ranging from 50 to 100 mg/kg, a rise in total bilirubin was observed in these patients. Moreover, liver enzymes (ALT and AST) increased moderately (p 0.0001). So, it is recommended to monitor total bilirubin and liver enzymes during the treatment with ceftriaxone, especially for a long duration (more than 5 days) or use another agent in patients with high baseline values.What is Known:• The dosing regimen of ceftriaxone (50 to 100 mg/kg) provided optimum therapeutic outcomes.• Some studies show data for total and free Ceftriaxone best fitted on a one-compartment model while other studies show data for total and free Ceftriaxone best fitted on a two-compartment model.What is New:• Up to my knowledge this is the first study ,considering individual pharmacokinetic analysis, conducted on hospitalized Egyptian pediatric population most of them with reduced kidney function with ages ranging from 2.5 months to 12 years. Data for total and free Ceftriaxone best fitted on a one-compartment model with linear clearance of the free ceftriaxone.• In all patients, total bilirubin and liver function tests were mildly increased, making them at risk for cholestasis or ceftriaxone-induced cholestatic hepatitis.

Delayed treatment with ceftriaxone reverses the enhanced sensitivity of TBI mice to chemically-induced seizures.

The pathophysiological changes that occur after traumatic brain injury (TBI) can lead to the development of post-traumatic epilepsy, a life-long complication of brain trauma. The etiology of post-traumatic epilepsy remains unknown, but TBI brains exhibit an abnormal excitatory / inhibitory balance. In this study, we examine how brain injury alters susceptibility to chemically-induced seizures in C57Bl/6J mice, and if pharmacological enhancement of glutamate transporters can reduce chronic post-traumatic seizures. We found that controlled cortical impact (CCI) mice display delayed susceptibility to pentylenetetrazol (PTZ)-induced seizures. While CCI mice have no change in seizure susceptibility at 7d post-injury (dpi), at 70dpi they have reduced latency to PTZ-induced seizure onset, higher seizure frequency and longer seizure duration. Quantification of glutamate transporter mRNA showed that levels of Scl1a2 and Scl1a3 mRNA were increased at 7dpi, but significantly decreased at 70dpi. To test if increased levels of glutamate transporters can ameliorate delayed-onset seizure susceptibility in TBI mice, we exposed a new cohort of mice to CCI and administered ceftriaxone (200mg/kg/day) for 14d from 55-70dpi. We found that ceftriaxone significantly increased Scl1a2 and Scl1a3 in CCI mouse brain at 70dpi, and prevented the susceptibility of CCI mice to PTZ-induced seizures. This study demonstrates cortical impact can induce a delayed-onset seizure phenotype in mice. Delayed (55dpi) ceftriaxone treatment enhances glutamate transporter mRNA in the CCI brain, and reduces PTZ-induced seizures in CCI mice.