ro13-9904 and Inflammation

Prevention of epilepsy is a great unmet need. Acute central nervous system (CNS) insults such as traumatic brain injury (TBI), cerebrovascular accidents (CVA), and CNS infections account for 15%-20% of all epilepsy. Following TBI and CVA, there is a latency of days to years before epilepsy develops. This allows treatment to prevent or modify postinjury epilepsy. No such treatment exists. In animal models of acquired epilepsy, a number of medications in clinical use for diverse indications have been shown to have antiepileptogenic or disease-modifying effects, including medications with excellent side effect profiles. These include atorvastatin, ceftriaxone, losartan, isoflurane, N-acetylcysteine, and the antiseizure medications levetiracetam, brivaracetam, topiramate, gabapentin, pregabalin, vigabatrin, and eslicarbazepine acetate. In addition, there are preclinical antiepileptogenic data for anakinra, rapamycin, fingolimod, and erythropoietin, although these medications have potential for more serious side effects. However, except for vigabatrin, there have been almost no translation studies to prevent or modify epilepsy using these potentially "repurposable" medications. We may be missing an opportunity to develop preventive treatment for epilepsy by not evaluating these medications clinically. One reason for the lack of translation studies is that the preclinical data for most of these medications are disparate in terms of types of injury, models within different injury type, dosing, injury-treatment initiation latencies, treatment duration, and epilepsy outcome evaluation mode and duration. This makes it difficult to compare the relative strength of antiepileptogenic evidence across the molecules, and difficult to determine which drug(s) would be the best to evaluate clinically. Furthermore, most preclinical antiepileptogenic studies lack information needed for translation, such as dose-blood level relationship, brain target engagement, and dose-response, and many use treatment parameters that cannot be applied clinically, for example, treatment initiation before or at the time of injury and dosing higher than tolerated human equivalent dosing. Here, we review animal and human antiepileptogenic evidence for these medications. We highlight the gaps in our knowledge for each molecule that need to be filled in order to consider clinical translation, and we suggest a platform of preclinical antiepileptogenesis evaluation of potentially repurposable molecu

Topics: Acetylcysteine; Animals; Anticonvulsants; Antioxidants; Atorvastatin; Brain Injuries, Traumatic; Ceftriaxone; Dibenzazepines; Drug Repositioning; Epilepsy; Epilepsy, Post-Traumatic; Erythropoietin; Fingolimod Hydrochloride; GABA Agents; Gabapentin; Humans; Immunologic Factors; Inflammation; Interleukin 1 Receptor Antagonist Protein; Isoflurane; Levetiracetam; Losartan; Neuroprotective Agents; Oxidative Stress; Pregabalin; Pyrrolidinones; Sirolimus; Stroke; Topiramate; Translational Research, Biomedical; Vigabatrin

Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality.. The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years.. The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome.. ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021.

Topics: Ceftriaxone; Double-Blind Method; Humans; Inflammation; Out-of-Hospital Cardiac Arrest; Pneumonia; Randomized Controlled Trials as Topic; Treatment Outcome

To explore the protective effect and mechanism of Bifidobacterium bifidum TMC3115 of improving the gut microbiota disorder caused by antibiotic exposurein early life, and the possible protection of inflammatory bowel disease in adulthood in mice.. 80 newborn mice were randomly divided into 3 groups, a blank control group(n=40), a ceftriaxone exposure group(n=20), a Bifidobacterium bifidum TMC3115 intervention group(n=20). After birth, they were respectively treated with saline, ceftriaxone(100 mg/kg), and ceftriaxone(100 mg/kg) + TMC3115(1×10~9CFU/d) for 3 weeks. After 3 weeks, half of each group was randomly sacrificed, and the rest were normally fed to 6 weeks. At 6 weeks, the blank control group was randomly divided into a negative control group(n=10) and a colitis model group(n=10). The negative control group drunk pure water freely, and the other three groups were added 3% DSS to the drinking water for 4 days to induce colitis. At 6 weeks and 4 days, the remaining mice were sacrificed. The weight change, spleen coefficient, gut microbiota analysis based on second-generation sequencing and serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-10(IL-10)levels of the mice at 3 weeks and after DSS intervention were recorded. In addition, the colon length and inflammation pathology score of the mice after DSS intervention were also measured.. At 3 weeks, compared with the control, antibiotic exposure in the early life inhibited the weight gain and reduced the diversity and uniformity of the gut microbiota of the mice(P<0.05). The intervention of TMC3115 under antibiotic exposure during this period increased the relative abundance of Bifidobacterium in the intestines(P<0.05), and the effect still existed after DSS stimulation in adulthood, laying the foundation for TMC3115 to exert long-term benefits. After DSS stimulation in adulthood, mice showed significant weight gain inhibition, colon length shorteningand inflammation pathology scoreincrease compared with the negative control(P<0.05), showed the inflammatory bowel disease(IBD)model was successfully constructed. The relative abundance of beneficial bacteria such as Lactobacillus in the Bifidobacterium bifidum TMC3115 intervention group increased compared with the ceftriaxone exposure group(P<0.05), while the relative abundance of harmful bacteria such as Staphylococcus, Clostridium, and Desulfovibrio decreased(P<0.05). Furthermore, the mice exposed to antibiotic in early life produced a stronger immune response, but the mice which received TMC3115 intervention at the same time had a significant decrease in serum TNF-α and IL-6 levels and increase in IL-10 level compared with the mice which only interfered with antibiotics(P<0.05).. Antibiotic exposure in early life is a negative factor for long-term inflammatory bowel disease, and TMC3115 has preventive significance for long-term inflammatory bowel disease under the background of antibiotic exposure. The mechanism of TMC3115 may be to adjust the gut microbiota and balance the immune system.

Topics: Animals; Anti-Bacterial Agents; Bifidobacterium bifidum; Ceftriaxone; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Inflammation; Inflammatory Bowel Diseases; Interleukin-10; Interleukin-6; Mice; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha; Weight Gain

Treatment of acute bacterial meningitis in children with bactericidal antibiotics causes cell wall lysis and a surge in inflammatory cascade, which in turn contributes to neuronal damage and morbidity. Pretreatment with a nonbacteriolytic antibiotic, such as rifampin, has been shown to attenuate the inflammatory response in experimental models of bacterial meningitis. In a pilot study, in children with bacterial meningitis, we have studied markers of inflammatory response and neuronal damage in 2 groups of children with bacterial meningitis; one group received rifampin pretreatment with ceftriaxone and the other group received ceftriaxone alone.. Forty children with bacterial meningitis, who were 3 months to 12 years of age, were randomly assigned to receive either a single dose rifampin (20 mg/kg) 30 minutes before ceftriaxone or ceftriaxone alone was given. The primary outcome variables were cerebrospinal fluid (CSF) concentrations of tumor necrosis factor alpha (TNFα), S100B and neuron-specific enolase on day 1 and day 5, and secondary outcome variables were the values of TNFα and interleukin 6 in serum on day 1 and day 5; hearing and neurologic sequelae at 3 months after recovery from the illness.. Children in rifampin pretreatment group had significantly lower CSF TNFα concentrations [median (interquartile range [IQR]): 15.5 (7.2-22.0) vs. 53.0 (9.0-87.5) pg/mL, P = 0.019] and S100B [median (IQR): 145.0 (54.7-450.0) vs. 447.5 (221.0-804.6) pg/mL, P = 0.033] on day 1 and S100B [median (IQR): 109.7 (64.0-287.0) vs. 322 (106.7-578.0) pg/mL, P = 0.048] and neuron-specific enolase [median (IQR): 8.6 (5-14.75) vs. 18.2 (7.0-28.75) ng/mL, P = 0.035] on day 5 when compared with ceftriaxone alone group. The rifampin-treated group also had reduced morbidity and neurologic sequelae; however, these were not statistically significant.. Pretreatment with single dose rifampin 30 minutes before ceftriaxone administration reduced the CSF concentrations of markers of inflammation and neuronal damage in children with bacterial meningitis.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Cranial Nerve Diseases; Humans; Infant; Inflammation; Interleukin-6; Meningitis, Bacterial; Phosphopyruvate Hydratase; Pilot Projects; Rifampin; S100 Calcium Binding Protein beta Subunit; Treatment Outcome; Tumor Necrosis Factor-alpha

Antibiotics used as a common clinical treatment have saved many lives. Widespread use of antibiotic therapy has been known to disrupt the balance of pathogenic bacteria, host-associated microorganisms and environment. However, our understanding of Bacillus licheniformis for health benefits and ability to restore the ceftriaxone sodium-induced gut microbial dysbiosis is severely limited. We used Caco-2 cell, H&E (hematoxylin-eosin staining), RT-PCR and 16S rRNA sequencing techniques to investigate the influence of Bacillus licheniformis on gut microbial dysbiosis and inflammation following ceftriaxone sodium treatment. The results showed that treatment of ceftriaxone sodium in 7 days suppressed the expression of Nf-κB pathway mRNA levels, which caused cytoplasmic vacuolization in intestinal tissues, afterward, the administration of Bacillus licheniformis could effectively restore intestinal morphology and inflammation levels. Moreover, the ceftriaxone sodium treatment entirely affected the intestinal microbial ecology, leading to a decrease in microbial abundance. Firmicutes, Proteobacteria, and Epsilonbacteraeota were the most predominant phyla in each of the four groups. Specifically, the MA group (ceftriaxone sodium treatment) resulted in a significant decrease in the relative abundance of 2 bacterial phyla and 20 bacterial genera compared to the administration of Bacillus licheniformis after ceftriaxone sodium treatment. The supplementation of Bacillus licheniformis could increase the growth of Firmicutes and Lactobacillus and encourage the construction of a more mature and stable microbiome. Furthermore, Bacillus licheniformis could restore the intestinal microbiome disorders and inflammation levels following ceftriaxone sodium treatment.

Topics: Animals; Anti-Bacterial Agents; Bacillus licheniformis; Bacteria; Caco-2 Cells; Ceftriaxone; Dysbiosis; Firmicutes; Gastrointestinal Microbiome; Humans; Inflammation; Mice; RNA, Ribosomal, 16S

The clinical efficacy of perioperative chemotherapy regimen (rifampicin, doxycycline, levofloxacin, ceftriaxone) was evaluated for lumbar brucellosis spondylitis patients with neurological injury.. In Beijing Ditan Hospital affiliated with Capital Medical University, 32 patients with lumbar brucellosis spondylitis underwent surgery and triple perioperative chemotherapy (rifampicin, doxycycline, levofloxacin) between 2011 and 2021 due to neurological injury, and 34 patients matched up with the triple group underwent rifampicin, doxycycline, levofloxacin, and ceftriaxone. Both groups were compared in terms of changes in inflammation index, low back/leg pain, lumbar function, neurological function, and adverse drug reactions.. There was no significant difference in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), low back pain visual analogue scale (VAS), leg pain VAS, lumbar Oswestry disability index (ODI) and nerve function injury rate between the two groups before chemotherapy (. For lumbar brucellosis spondylitis with neurological injury, quadruple perioperative chemotherapy of rifampicin, doxycycline, levofloxacin and ceftriaxone can significantly reduce perioperative inflammation, and improve low back/leg pain, as well as promoting neurological function recovery in the short term.

Topics: Brucellosis; Ceftriaxone; Doxycycline; Humans; Inflammation; Levofloxacin; Low Back Pain; Lumbar Vertebrae; Retrospective Studies; Rifampin; Spondylitis; Treatment Outcome

Subcutaneous administration is a novel way to deliver antibiotics for an infection, but intolerability has been reported. Evaluating the local tolerability of subcutaneously administered antibiotics is not standardized. The goal of this study was to develop an animal model to assess the subcutaneous administration of ceftriaxone. Sprague-Dawley rats were given daily subcutaneous injections for 12 days. The back of each animal was divided into 4 quadrants, with injections rotating each day among the quadrants. Ceftriaxone (1,000 mg/kg of body weight daily) was given in different concentrations and durations. Normal saline and potassium chloride solutions (2 meq/2 ml) were used as negative and positive controls, respectively. After the treatment course, skin samples were biopsied, and the local inflammatory response was assessed histologically using a semiquantitative scoring system. The histopathology scores were compared using a Kruskal-Wallis test. Injections with potassium chloride resulted in full-thickness skin necrosis with subcutaneous atrophy that was not seen in the saline-injected animals; inflammation of the muscular panniculus was observed, with various degrees of myocyte injury. Serosanguinous cavity formation in the subcutaneous compartment was observed when ceftriaxone (125 mg/ml) was given as a bolus injection, but the extent of the local tissue response was remarkably reduced when the same ceftriaxone dose was given at a lower concentration (25 mg/ml) over 120 min (

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Female; Inflammation; Injections, Subcutaneous; Male; Rats; Rats, Sprague-Dawley

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Ceftriaxone; Coronavirus Infections; COVID-19; Diagnosis, Differential; Erythema Multiforme; Humans; Inflammation; Male; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

Ceftriaxone (CTX) is a third-generation cephalosporin antibiotic that has broad-spectrum antimicrobial activity. This agent also has anti-inflammatory and antioxidant characteristics. In the current study, the effects of CTX against hepatorenal damages in a D-galactose (DGL) induced aging model were investigated. We used twenty-eight male mice which equally and randomly were separated into four groups as follows: Control, DGL group (treated with 500 mg/kg/day DGL orally for six weeks), DGL + CTX group (treated with 500 mg/kg/day DGL orally plus 200 mg/kg/day CTX intraperitoneally for six weeks), and CTX group (treated with 200 mg/kg/day CTX intraperitoneally for six weeks). The liver and kidney function indices such as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase were measured. Also, levels of malondialdehyde, catalase, and glutathione peroxidase in hepatic and renal tissues were evaluated. Moreover, the expression profiles of interleukin 1 beta and tumor necrosis factor alpha were assessed. The liver and kidney tissues were assessed for histopathological lesions. The results showed that aging induced by DGL leads to abnormalities in functional indices of the liver and kidneys. DGL also induced significant oxidative stress and inflammation, as well as histopathological lesions, in these organs. CTX improved functional indices, as well as the parameters of oxidative stress and inflammation, compared with the DGL-treated animals. These results were also confirmed by histological evaluations of the liver and kidneys. These data provide evidence for the therapeutic value of CTX in clinical practice for mitigating the hepatorenal damages of aging.

Topics: Aging; Animals; Ceftriaxone; Galactose; Hepatorenal Syndrome; Inflammation; Kidney; Liver; Male; Mice; Oxidation-Reduction; Oxidative Stress

The objective of this study was to compare the release of endotoxin and pro-inflammatory cytokines as well as pregnancy outcomes after antibiotic exposure in healthy and bacterial infected pregnant rats. Thirty female Wistar pregnant rats were divided into five groups. Group A considered as control and received intraperitoneal saline 0.9% on 17th day of gestation or DG) and groups B and C treated with 20 mg/kg/day intravenous ceftriaxone and ceftazidime, respectively (DG: 18-20). Groups D and E received intraperitoneal E. coli and LPS on 17th DG respectively. Also, groups F and G received the same treatment as group D but they treated with the exact antibiotics mentioned for groups B and C (same dose and duration). Pregnancy outcomes as well as maternal sera levels of endotoxin, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 were assessed using enzyme-linked immunosorbent assay. It was shown that group B had a higher IL-1β (P = 0.003) and TNF-α (P = 0.003) levels compared to the controls (CTC). Group C expressed a lower gestational duration (P = 0.007) as well as higher IL-6 (P = 0.025) and TNF-α (P < 0.001) levels CTC. Interestingly, both group B (P = 0.021) and C (P < 0.001) had a higher rate of endotoxin release CTC. Moreover, in group C, IL-6 (P < 0.0001 and r = -0.941) had a significant correlation with gestational duration. As the results showed, antibiotic administration in non-indication condition seems to be associated with significantly higher production of endotoxin and inflammatory cytokines which increase the risk of poor pregnancy outcomes.

Topics: Administration, Intravenous; Animals; Animals, Newborn; Anti-Bacterial Agents; Birth Weight; Ceftazidime; Ceftriaxone; Endotoxins; Female; Gene Expression Regulation; Gestational Age; Inflammation; Interleukin-1beta; Interleukin-6; Pregnancy; Pregnancy Outcome; Rats, Wistar; Tumor Necrosis Factor-alpha

Epidemiological studies revealed that antibiotics exposure increases a risk of inflammatory bowel diseases (IBD) development. It remained largely unknown how antibiotic-induced dysbiosis confers the risk for enhanced inflammatory response. The aim of the present study was to test the hypothesis that SCFAs, their receptors and transporters mediate the antibiotic long-term effects on the functional state of colonic mucosa and susceptibility to the experimental colitis. Male Wistar rats were treated daily for 14 days with antibiotic ceftriaxone (300 mg/kg, i.m.) or vehicle; euthanized by CO2 inhalation followed by cervical dislocation in 1, 14 or 56 days after antibiotic withdrawal. We found increased cecum weight and sustained changes in microbiota composition after ceftriaxone treatment with increased number of conditionally pathogenic enterobacteria, E. coli, Clostridium, Staphylococcus spp. and hemolytic bacteria even at 56 days after antibiotic withdrawal. The concentration of SCFAs was decreased after ceftriaxone withdrawal. We found decreased immunoreactivity of the FFA2, FFA3 receptors, SMCT1 and increased MCT1 & MCT4 transporters of SCFAs in colon mucosa. These changes evoked a significant shift in colonic mucosal homeostasis: the disturbance of oxidant-antioxidant balance; activation of redox-sensitive transcription factor HIF1α and ERK1/2 MAP kinase; increased colonic epithelial permeability and bacterial translocation to blood; morphological remodeling of the colonic tissue. Ceftriaxone pretreatment significantly reinforced inflammation during experimental colitis 56 days after ceftriaxone withdrawal, which was confirmed by increased histopathology of colitis, Goblet cell dysfunction, colonic dilatation and wall thickening, and increased serum levels of inflammatory cytokines (TNF-α and IL-10). Since the recognition of the importance of microbiota metabolic activity rather than their composition in the development of inflammatory disorders, e.g. IBD, the present study is the first report on the role of the SCFA system in the long lasting side effects of antibiotic treatment and its implication in IBD development.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Colitis; Colon; Cytokines; Dysbiosis; Fatty Acids, Volatile; Gastrointestinal Microbiome; Homeostasis; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Male; Rats; Rats, Wistar

Sepsis is a life-threatening systemic inflammatory condition triggered as a result of an excessive host immune response to infection. In the past, immunomodulators have demonstrated a protective effect in sepsis. Azithromycin (a macrolide antibiotic) has immunomodulatory activity and was therefore evaluated in combination with ceftriaxone in a clinically relevant murine model of sepsis induced by cecal ligation and puncture (CLP). First, mice underwent CLP and 3 h later were administered the vehicle or a subprotective dose of ceftriaxone (100 mg/kg of body weight subcutaneously) alone or in combination with an immunomodulatory dose of azithromycin (100 mg/kg intraperitoneally). Survival was monitored for 5 days. In order to assess the immunomodulatory activity, parameters such as plasma and lung cytokine (interleukin-6 [IL-6], IL-1β, tumor necrosis factor alpha) concentrations, the plasma glutathione (GSH) concentration, plasma and lung myeloperoxidase (MPO) concentrations, body temperature, blood glucose concentration, and total white blood cell count, along with the bacterial load in blood, peritoneal lavage fluid, and lung homogenate, were measured 18 h after CLP challenge. Azithromycin in the presence of ceftriaxone significantly improved the survival of CLP-challenged mice. Further, the combination attenuated the elevated levels of inflammatory cytokines and MPO in plasma and lung tissue and increased the body temperature and blood glucose and GSH concentrations, which were otherwise markedly decreased in CLP-challenged mice. Ceftriaxone produced a significant reduction in the bacterial load, while coadministration of azithromycin did not produce a further reduction. Therefore, the survival benefit offered by azithromycin was due to immunomodulation and not its antibacterial action. The findings of this study indicate that azithromycin, in conjunction with appropriate antibacterial agents, could provide clinical benefits in sepsis.

Topics: Animals; Azithromycin; Bacterial Load; Ceftriaxone; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Glutathione; Inflammation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Lung; Mice; Sepsis; Tumor Necrosis Factor-alpha

Bacterial biofilms provoke and/or promote the most chronic and recurrent infectious diseases. Previously, experimental models of purulent peritonitis and meningoencephalitis revealed positive antibiofilm effect of metallic nanoparticles and the absence of resistance against such nanoparticles in microorganisms. This study examines the combined effect of silver nanoparticles with ceftriaxone and methyluracil on recovery mechanisms during inflammatory diseases exemplified by purulent peritonitis in experimental animals.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Ceftriaxone; Infectious Disease Medicine; Inflammation; Male; Meningoencephalitis; Metal Nanoparticles; Peritonitis; Rats; Rats, Wistar; Recurrence; Silver; Uracil

Topics: Abscess; Animals; Anti-Bacterial Agents; Ceftriaxone; Cicatrix; Humans; Hydronephrosis; Inflammation; Kidney; Kidney Function Tests; Male; Mice, Inbred C3H; Pyelonephritis; Treatment Outcome

Maxillofacial traumatic injuries concomitant with craniocerebral trauma are still considered as an actual problem in emergency medicine. For this category of patients one of the dangerous and severe complications is development of inflammatory process in the injured areas. Fracture lines of upper and middle facial zones pass through the accessory sinuses of the nose, maxillary/upper dental arch area and are considered to be open and infected fractures. Combination of these fractures with craniocerebral injuries and especially, with open traumas creates predisposition for development of inflammatory processes in CNS that can result in heavy outcome. 29 patients (among them 5-females and 24 -males) with severe and open craniofacial fractures were observed by the authors. For prevention of inflammatory complications in complex treatment of the patients, intra-arterial infusions of therapeutic agents (wide spectrum of antibiotics, Heparin) were used for stimulation of reparative regeneration in fractured fragments of facial bones. After the main surgical interventions (neurosurgery, surgery of facial bones) sanitation of infected centers (accessory sinuses of the nose, oral cavity) and catheterization of external carotid arteries through the temporal arteries were performed. According to the severity of the trauma and its preferential localization, catheterization of carotid arteries was conducted unilaterally (12 cases) or bilaterally (17 cases). Insertion depth through femoral artery was 6-8 cm. Catheter was stayed in the artery for 7-8 days. Intra-arterial infusions were carried out in the morning and evening. Therapeutic agents for arterial infusion included: antibiotic (Rocephin and its analogues), Heparin. To determine the effectiveness of vascular therapy dopplerography of external carotid artery, its branches and supratrochlear artery was performed. Dopplerography of supratrochlear artery, which is the branch of internal carotid artery, was conducted to detect the impact of therapeutic agents, administered in external carotid artery, on the internal carotid artery. During the treatment of complicated concomitant craniofacial injuries in a sequential order, development of inflammatory processes was not observed even in the patients with basic inflammatory processes in accessory sinuses of the nose. After infusion of therapeutic agents to external carotid artery, dopplerographically, sharp increase in blood flow in main artery and its branches, indicate

Topics: Anti-Bacterial Agents; Anticoagulants; Carotid Artery, External; Ceftriaxone; Craniocerebral Trauma; Face; Female; Heparin; Humans; Inflammation; Infusions, Intra-Arterial; Male; Maxillofacial Injuries; Postoperative Complications; Ultrasonography, Doppler

Lyme borreliosis is a disease transmitted by ticks to mammals, especially in horses and humans. Caused by a spirochete Borrelia burgdorferi, it can result in lameness, arthritis, carditis, dermatitis and neurological signs. Anaphylactoid reactions are severe responses caused by direct action of substances (drugs, toxins), which can pose risks to life. Still poorly documented in horses, these reactions are caused by the effects of inflammatory mediators such as histamine, kinins and arachidonic acid metabolites. The last two are the most clinically relevant for the species.. The simultaneous occurrence of anaphylactoid reaction in two horses experimentally infected by Borrelia burgdorferi undergoing intravenous treatment with ceftriaxone sodium is reported. It was administered 4.7 × 10(8) spirochetes intradermal and subcutaneous applications in both horses to evaluate clinical aspects of the Lyme disease, 95 days before the application of sodium ceftriaxone. During the administration, one horse (a gelding) showed immediate and severe anaphylactoid symptoms such as urticaria, dyspnea, tachycardia, and eyelid edema, which were controlled by injecting dexamethasone. After 1 day, it expressed signs of abdominal discomfort, caused by severe bloat, which was treated surgically via celiotomy. Subsequently, this gelding had piroplasmosis and severe anemia, requiring treatment with an antimicrobial and blood transfusion. Second horse (a mare) showed signs of hypotension during the application of the antibiotic, which disappeared only when the application was interrupted. Days after the event, the mare developed moderate large colon bloat, which was treated with medication only. Subsequently the mare was evolved into the prodromal phase of laminitis in one of the forelimbs, which was treated for 10 days with non-steroidal anti-inflammatory and rheology modifying drugs and cryotherapy.. From the two cases presented here, it does appear that sodium ceftriaxone can induce anaphylactoid reactions in horses infected by Borrelia burgdorferi, which may evolve into colic syndrome, laminitis and the occurrence of opportunistic infections. However, further evidence should be collected in order to draw definite conclusions.

Topics: Adrenal Cortex Hormones; Anaphylaxis; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Borrelia burgdorferi; Ceftriaxone; Colic; Dexamethasone; Female; Foot Diseases; Hoof and Claw; Horse Diseases; Horses; Inflammation; Lyme Disease; Male

The β-lactam antibiotic ceftriaxone stimulates glutamate transporter GLT-1 expression and is effective in neuropathic and visceral pain models. This study examined the effects of ceftriaxone and its interactions with different analgesics (ibuprofen, celecoxib, paracetamol, and levetiracetam) in somatic and visceral pain models in rodents.. The effects of ceftriaxone (intraperitoneally/intraplantarly), analgesics (orally), and their combinations were examined in the carrageenan-induced paw inflammatory hyperalgesia model in rats (n = 6-12) and in the acetic acid-induced writhing test in mice (n = 6-10). The type of interaction between ceftriaxone and analgesics was determined by isobolographic analysis.. Pretreatment with intraperitoneally administered ceftriaxone (10-200 mg/kg per day) for 7 days produced a significant dose-dependent antihyperalgesia in the somatic inflammatory model. Acute administration of ceftriaxone, via either intraperitoneal (10-200 mg/kg) or intraplantar (0.05-0.2 mg per paw) routes, produced a significant and dose-dependent but less efficacious antihyperalgesia. In the visceral pain model, significant dose-dependent antinociception of ceftriaxone (25-200 mg/kg per day) was observed only after the 7-day pretreatment. Isobolographic analysis in the inflammatory hyperalgesia model revealed approximately 10-fold reduction of doses of both drugs in all examined combinations. In the visceral nociception model, more than 7- and 17-fold reduction of doses of both drugs was observed in combinations of ceftriaxone with ibuprofen/paracetamol and celecoxib/levetiracetam, respectively.. Ceftriaxone exerts antihyperalgesia/antinociception in both somatic and visceral inflammatory pain. Its efficacy is higher after a 7-day pretreatment than after acute administration. The two-drug combinations of ceftriaxone and the nonsteroidal analgesics/levetiracetam have synergistic interactions in both pain models. These results suggest that ceftriaxone, particularly in combinations with ibuprofen, celecoxib, paracetamol, or levetiracetam, may provide useful approach to the clinical treatment of inflammation-related pain.

Topics: Acetaminophen; Analgesics; Analgesics, Non-Narcotic; Animals; Anti-Bacterial Agents; Ceftriaxone; Celecoxib; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Hyperalgesia; Ibuprofen; Inflammation; Levetiracetam; Male; Pain; Piracetam; Pyrazoles; Rats; Rats, Wistar; Sulfonamides

A 90-year-old woman presented with subacute painless left ptosis. Examination of the left eye revealed ptosis with loss of the superior eyelid sulcus, 2 mm of proptosis, mild tenderness with retropulsion, and optic disc edema. Levator function and extraocular movements were normal, and there was no relative afferent pupillary defect. MRI demonstrated thickening of the extraocular muscles in the left orbit with lacrimal gland enlargement and mild enhancement of the optic nerve sheath. Serology revealed a positive enzyme-linked immunosorbent assay for Lyme antibodies and a positive Western blot of Lyme IgG titer. The patient recalled a tick bite 6 months earlier, at which time Lyme serologies were negative. After 3 weeks of intravenous ceftriaxone, she had a significant improvement and a full recovery by 3 months. Lyme disease should be included in the differential diagnosis of orbital inflammation, especially in Lyme-endemic areas.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Blepharoptosis; Ceftriaxone; Female; Functional Laterality; Humans; Inflammation; Lyme Disease; Magnetic Resonance Imaging; Orbit

Exacerbation of cerebrospinal fluid (CSF) inflammation in response to bacteriolysis by beta-lactam antibiotics contributes to brain damage and neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic acting on Gram-positive bacteria, lessens inflammation and brain injury compared to ceftriaxone. With a view to a clinical application for pediatric bacterial meningitis, we investigated the effect of combining daptomycin or rifampin with ceftriaxone in an infant rat pneumococcal meningitis model. Eleven-day-old Wistar rats with pneumococcal meningitis were randomized to treatment starting at 18 h after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed 15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22 h after the initiation of therapy and was assessed for concentrations of defined chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h after infection and hearing loss was assessed at 3 weeks after infection. Daptomycin plus ceftriaxone versus ceftriaxone significantly (P < 0.04) lowered CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and interleukin 6 (IL-6) at 6 h and MIP-1α, IL-6, and IL-10 at 22 h after initiation of therapy, led to significantly (P < 0.01) less apoptosis, and significantly (P < 0.01) improved hearing capacity. While rifampin plus ceftriaxone versus ceftriaxone also led to lower CSF inflammation (P < 0.02 for IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity. Adjuvant daptomycin could therefore offer added benefits for the treatment of pediatric pneumococcal meningitis.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Brain Damage, Chronic; Ceftriaxone; Chemokines; Cytokines; Daptomycin; Drug Administration Schedule; Drug Therapy, Combination; Hearing Loss; Inflammation; Meningitis, Pneumococcal; Random Allocation; Rats; Rats, Wistar; Rifampin

Antibiotic-induced bacteriolysis exacerbates inflammation and brain damage in bacterial meningitis. Here the quality and temporal kinetics of cerebrospinal fluid (CSF) inflammation were assessed in an infant rat pneumococcal meningitis model for the nonbacteriolytic antibiotic daptomycin versus ceftriaxone. Daptomycin led to lower CSF concentrations of interleukin 1beta (IL-1beta), IL-10, IL-18, monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1 alpha (MIP-1alpha) (P < 0.05). In experimental pneumococcal meningitis, daptomycin treatment resulted in more rapid bacterial killing, lower CSF inflammation, and less brain damage than ceftriaxone treatment.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Ceftriaxone; Cerebrospinal Fluid; Daptomycin; Disease Models, Animal; Humans; Inflammation; Meningitis, Pneumococcal; Rats; Rats, Wistar; Treatment Outcome

To evaluate the penetration of ceftriaxone into the cerebrospinal fluid (CSF) in patients with invasive bacterial infection and to define correlation between the penetration and laboratory markers of inflammation.. Levels of ceftriaxone in the serum and CSF of 17 patients with purulent meningitis were examined. Serum concentrations of ceftriaxone before and after its administration were measured in 9 patients (18 samples, 52.9 %) by microbiological assay based on the agar diffusion test. In all patients, the CSF/serum quotient for ceftriaxone was calculated and correlated with laboratory markers of inflammation (C-reactive protein, fibrinogen and neutrophils). The CSF from nine patients with positive culture for bacteria was used for a modified bactericidal test.. Ceftriaxone levels in the serum before and after administration (31.2 mg/l -/+ SD 12.29 and 300.0 mg/l -/+ SD 125.9, respectively) were different (p = 0.000156). The decrease of ceftriaxone levels in the CSF was gradual. There was also a significant difference between the levels of inflammatory markers and CSF/serum quotient of ceftriaxone. Patients with the values higher than 0.1 had higher CRP serum levels (p = 0.00192), fibrinogen serum levels (p = 0.0178) as well as neutrophil count in the CSF (p = 0.0112). However, no inflammatory markers (or their combinations) predicted the extent of penetration of ceftriaxone into the CSF.. High serum concentration of ceftriaxone causes higher penetration through the inflamed blood-brain barrier. Higher antibiotic penetration correlated with the extent of systemic inflammatory response. However, no inflammatory marker predicted the rate of ceftriaxone crossing the blood-brain barrier. Ceftriaxone penetration, with a 24-hour regimen of administration, remains reliable and efficient therapy of purulent meningitis.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; C-Reactive Protein; Ceftriaxone; Female; Fibrinogen; Humans; Inflammation; Interleukin-6; Male; Meningitis, Bacterial; Middle Aged; Young Adult

Zirconium molybdate gel was prepared by mixing (99)Mo, produced from (98)Mo(n,gamma) reaction and Zr solutions in nitrate media with excess H(2)O(2), and used as the base material for (99)Mo/(99m)Tc generator. The prepared generator showed a good performance. (99m)Tc eluted from the prepared generator passed the quality control tests with specifications meeting the requirements of European and US Pharmacopeias. The (99m)Tc eluate was used for labeling of cephalosporin analogue, ceftriaxone, which was then assessed for infection imaging in a mouse model. (99m)Tc-ceftriaxone was prepared at pH 9 with a radiochemical yield of 95+/-2% by adding (99m)Tc to 30 mg ceftriaxone in the presence of 50 microg SnCl(2).2H(2)O. Biodistribution studies in mice were carried out using experimentally induced infection in the left thigh using E. coli. Both thighs of the mice were dissected and counted to evaluate the ratio of bacterial infected thigh/contralateral thigh. (99m)Tc-ceftriaxone showed high uptake in the infectious lesion (T/NT =5.6+/-0.6 at 4h post injection). The abscess to normal muscle ratio indicated that (99m)Tc-ceftriaxone could be used for infection imaging. Besides, in vitro studies showed that (99m)Tc-ceftriaxone can differentiate between bacterial infection and sterile inflammation.

Topics: Animals; Bacterial Infections; Ceftriaxone; Escherichia coli Infections; Inflammation; Mice; Molybdenum; Muscle, Skeletal; Organotechnetium Compounds; Radionuclide Imaging; Technetium; Tissue Distribution; Zirconium

To examine the routes, dynamics and correlates of cochlear inflammation in meningitis to provide information on the pathogenesis of the associated hearing loss and indications for rational pharmacotherapeutical intervention.. A well-established rat model of Streptococcus pneumoniae meningitis was employed.. Eight rats were inoculated intrathecally and not treated, whereas 26 were inoculated and treated with ceftriaxone. Six rats were sham-inoculated, making a total of 40 rats. The rats were sacrificed when reaching terminal illness or after 7 days, followed by light microscopy. Routes of cochlear inflammatory infiltration were examined. The volume fraction of inflammatory infiltration was estimated and correlated to bacterial and leukocyte counts in cerebrospinal fluid (CSF) and blood.. The perilymphatic space was infiltrated with inflammatory cells via cochlear aqueduct, whereas the endolymphatic space was infiltrated from the spiral ligament. Rosenthal's canal was infiltrated through osseous spiral lamina canaliculi. In the untreated group, the degree of inflammation correlated with time of death, whereas antibiotic treatment reversed this development. Perilymphatic inflammation correlated significantly with the CSF leukocyte count, whereas endolymphatic inflammation correlated with spiral ligament inflammation.. Meningogenic inflammation of the rat cochlea occurs via the cochlear aqueduct and the spiral ligament capillary bed. The spiral ganglion is infiltrated through the osseous spiral lamina. The degree of inflammation correlates positively with time of death in untreated meningitis, whereas antibiotic treatment leads to subsiding infiltration during recovery.

Topics: Animals; Biopsy, Needle; Ceftriaxone; Cerebrospinal Fluid; Cochlear Diseases; Disease Models, Animal; Immunohistochemistry; Inflammation; Leukocyte Count; Male; Meningitis, Pneumococcal; Microscopy, Electron; Random Allocation; Rats; Rats, Wistar; Sensitivity and Specificity

In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), impairment of glial "Excitatory Amino Acid Transporters" (EAATs) together with an excess glutamate-release by invading immune cells causes excitotoxic damage of the central nervous system (CNS). In order to identify pathways to dampen excitotoxic inflammatory CNS damage, we assessed the effects of a beta-lactam antibiotic, ceftriaxone, reported to enhance expression of glial EAAT2, in "Myelin Oligodendrocyte Glycoprotein" (MOG)-induced EAE. Ceftriaxone profoundly ameliorated the clinical course of murine MOG-induced EAE both under preventive and therapeutic regimens. However, ceftriaxone had impact neither on EAAT2 protein expression levels in several brain areas, nor on the radioactive glutamate uptake capacity in a mixed primary glial cell-culture and the glutamate-induced uptake currents in a mammalian cell line mediated by EAAT2. Moreover, the clinical effect of ceftriaxone was preserved in the presence of the EAAT2-specific transport inhibitor, dihydrokainate, while dihydrokainate alone caused an aggravated EAE course. This demonstrates the need for sufficient glial glutamate uptake upon an excitotoxic autoimmune inflammatory challenge of the CNS and a molecular target of ceftriaxone other than the glutamate transporter. Ceftriaxone treatment indirectly hampered T cell proliferation and proinflammatory INFgamma and IL17 secretion through modulation of myelin-antigen presentation by antigen-presenting cells (APCs) e.g. dendritic cells (DCs) and reduced T cell migration into the CNS in vivo. Taken together, we demonstrate, that a beta-lactam antibiotic attenuates disease course and severity in a model of autoimmune CNS inflammation. The mechanisms are reduction of T cell activation by modulation of cellular antigen-presentation and impairment of antigen-specific T cell migration into the CNS rather than or modulation of central glutamate homeostasis.

Topics: Amino Acid Transport System X-AG; Animals; Anti-Bacterial Agents; beta-Lactams; Ceftriaxone; Central Nervous System; Encephalomyelitis, Autoimmune, Experimental; Female; Humans; Inflammation; Mice; Mice, Inbred C57BL; Models, Biological; Multiple Sclerosis; Neuroglia; Rats

The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A 2A adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis.. Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (Escherichia coli or Staphylococcus aureus) or lipopolysaccharide (LPS). Mice inoculated with live bacteria were treated with an A 2A AR agonist (ATL313) or phosphate buffered saline (PBS), with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days.. There was a significant survival benefit in mice infected with live E. coli (100% vs. 20%, p = 0.013) or S. aureus (60% vs. 20%, p = 0.02) when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, p = 0.005). The serum concentrations of TNF-alpha, MIP-1 alpha, MCP-1, IFN-gamma, and IL-17 were decreased by ATL313 after LPS injection (p < 0.05). Additionally, ATL313 increased the concentration of IL-10 under the same conditions (p < 0.05). Circulating white blood cell concentrations were higher in ATL313 treated animals (p < 0.01).. Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.

Topics: Animals; Anti-Inflammatory Agents; Ceftriaxone; Cytokines; Disease Models, Animal; Escherichia coli Infections; Female; Inflammation; Leukocytes; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Piperidines; Receptor, Adenosine A2A; Sepsis; Staphylococcal Infections; Survival Analysis

Bacteriolytic antibiotics cause the release of bacterial components that augment the host inflammatory response, which in turn contributes to the pathophysiology of brain injury in bacterial meningitis. In the present study, antibiotic therapy with nonbacteriolytic daptomycin was compared with that of bacteriolytic ceftriaxone in experimental pneumococcal meningitis, and the treatments were evaluated for their effects on inflammation and brain injury. Eleven-day-old rats were injected intracisternally with 1.3 x 10(4) +/- 0.5 x 10(4) CFU of Streptococcus pneumoniae serotype 3 and randomized to therapy with ceftriaxone (100 mg/kg of body weight subcutaneously [s.c.]; n = 55) or daptomycin (50 mg/kg s.c.; n = 56) starting at 18 h after infection. The cerebrospinal fluid (CSF) was assessed for bacterial counts, matrix metalloproteinase-9 levels, and tumor necrosis factor alpha levels at different time intervals after infection. Cortical brain damage was evaluated at 40 h after infection. Daptomycin cleared the bacteria more efficiently from the CSF than ceftriaxone within 2 h after the initiation of therapy (log(10) 3.6 +/- 1.0 and log(10) 6.3 +/- 1.4 CFU/ml, respectively; P < 0.02); reduced the inflammatory host reaction, as assessed by the matrix metalloproteinase-9 concentration in CSF 40 h after infection (P < 0.005); and prevented the development of cortical injury (cortical injury present in 0/30 and 7/28 animals, respectively; P < 0.004). Compared to ceftriaxone, daptomycin cleared the bacteria from the CSF more rapidly and caused less CSF inflammation. This combined effect provides an explanation for the observation that daptomycin prevented the development of cortical brain injury in experimental pneumococcal meningitis. Further research is needed to investigate whether nonbacteriolytic antibiotic therapy with daptomycin represents an advantageous alternative over current bacteriolytic antibiotic therapies for the treatment of pneumococcal meningitis.

Topics: Animals; Anti-Bacterial Agents; Brain Injuries; Ceftriaxone; Cerebral Cortex; Cerebrospinal Fluid; Daptomycin; Disease Models, Animal; Humans; Inflammation; Meningitis, Pneumococcal; Random Allocation; Rats; Treatment Outcome

Anti-inflammatory therapy with interleukin-10 (IL-10) was previously reported to reduce pulmonary inflammation and to prevent septicaemia in murine pneumococcal pneumonia treated with ceftriaxone. In the present report, we investigated the influence of pulmonary infection and IL-10 administration on the pharmacokinetics of ceftriaxone.. CD1 mice were infected with 10(7) cfu of Streptococcus pneumoniae. Treatments (intraperitoneal) with IL-10 (1 microg per mouse), ceftriaxone (20 mg/kg) or the combination of IL-10 + ceftriaxone were initiated 18 h after infection. Groups of mice were sacrificed at several time points from 5 min to 24 h after initiation of therapy. Ceftriaxone was quantified in blood and lungs using a microbiological assay. Additional groups of mice received a second dose of IL-10 at 36 h post-infection. Survival rates were recorded over 14 days.. The clearance of ceftriaxone was significantly reduced in infected mice compared with that in non-infected animals (P < 0.01), whereas AUC, mean residence time, t(1/2) and AUC(lung)/AUC(serum) were significantly enhanced (P < 0.01, 0.01, 0.05, 0.05). Co-administration of IL-10 with ceftriaxone in infected animals further retained ceftriaxone in the bloodstream and reduced its volume of distribution at steady state and the ratio of AUC(lung)/AUC(serum). IL-10 alone did not modify significantly the pharmacokinetics of ceftriaxone in blood and lungs of non-infected animals.. The results suggest that pulmonary infection, and therapy with IL-10, both affect the pharmacokinetics of ceftriaxone. Indeed, administration of IL-10 + ceftriaxone improved the survival rate of mice (P < 0.001 compared with therapy with ceftriaxone alone). IL-10 should be considered as an adjunctive therapy to antibiotics against severe infections.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Drug Therapy, Combination; Female; Inflammation; Interleukin-10; Lung; Mice; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial wall components. TLR2 function was investigated in a murine Streptococcus pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. TLR2(-/-) mice showed earlier time of death than wt mice (P<.02). Plasma interleukin-6 levels and bacterial numbers in blood and peripheral organs were similar for both strains. With ceftriaxone therapy, none of the wt but 27% of the TLR2(-/-) mice died (P<.04). Beyond 3 hours after infection, TLR2(-/-) mice had higher bacterial loads in brain than did wt mice, as assessed with luciferase-tagged S. pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera. After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of TLR2(-/-) than wt mice (P<.05) and was related to increased blood-brain barrier permeability (Evans blue staining, P<.02). In conclusion, the lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.

Topics: Animals; Ceftriaxone; Cephalosporins; Disease Models, Animal; Disease Susceptibility; Drosophila Proteins; Inflammation; Listeria monocytogenes; Listeriosis; Membrane Glycoproteins; Meningitis, Bacterial; Mice; Mice, Inbred C57BL; Mice, Knockout; Pneumococcal Infections; Receptors, Cell Surface; Streptococcus pneumoniae; Time Factors; Toll-Like Receptor 2; Toll-Like Receptors

To try efficacy and safety of ophramax (cephtriaxon) made in India ("Ranbaxy") in infectious-inflammatory diseases treated in a general hospital.. Ophramax was given in a dose 1 to 4 g/day to 23 patients with pneumonia, chronic bronchitis, soft tissue infection, enterocolitis, etc. Therapeutic effect was examined with bacteriological identification of the infective agents, antibioticograms, agar diffusion test.. High sensitivity of pathogens to ophramax was observed in bronchopulmonary diseases (90.7%). In other infections sensitivity of the pathogens was 59.3%. Enterococci were the only highly resistant pathogens (40.5%). Ophramax remains in the body in sufficiently high concentrations for 24 hours. This attributes to good therapeutic effect.. Clinico-microbiological and pharmacokinetic findings show that ophramax can be used as a basic drug for treatment of different infectious-inflammatory diseases. Once-a-day regimen is a great advantage of ophramax.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Ceftriaxone; Cephalosporins; Drug Monitoring; Drug Resistance, Bacterial; Humans; Inflammation; Middle Aged

No universally recognized agent is available for prophylaxis or therapy of mucositis induced by chemotherapy or chemo-radiotherapy. The effect of clarithromycin on the severity of mucositis induced by cyclophosphamide was investigated using a mouse model. Four cross-sections of small intestine (levels A, B, C, and D) were taken at equivalent intervals at day 5 after cyclophosphamide (400 mg kg(-1)) administration. The sections were stained with haematoxylin and eosin, and were graded for the degree of mucositis histologically. At section level B, the number of mice with no mucositis (grade 0) in the clarithromycin group was significantly greater than that in the ceftriaxone group (P<0.05). At levels B and C, the number of mice with no mucositis (grade 0) in the clarithromycin group was significantly greater than that in the normal saline (NS) group (P<0.05). At level C, the number of mice with grade 2 mucositis in the ceftriaxone group was significantly greater than that in the NS group (P<0.05). When the number of sections at all levels were analyzed together, the number of mice with no mucositis (grade 0) in the clarithromycin group was significantly greater than that in the ceftriaxone and NS groups (P<0.05). The present observation suggests that clarithromycin and ceftriaxone attenuates and aggravates cyclophosphamide-induced mucositis. It prompts clinical trials in bone marrow transplant (BMT) recipients receiving cyclophosphamide for conditioning, and reconsideration in the use of ceftriaxone in the treatment of neutropenic fever in BMT recipients.

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents, Alkylating; Ceftriaxone; Clarithromycin; Cyclophosphamide; Dose-Response Relationship, Drug; Female; Inflammation; Intestinal Mucosa; Mice; Mice, Inbred BALB C

Interleukin (IL)-10 is a biologically active anti-inflammatory and immunomodulatory cytokine. The respective effects or combined effect of ceftriaxone (Ctri) and IL-10 on host response was studied in a mouse model of lethal pneumococcal pneumonia. A once daily intraperitoneal (ip) injection of IL-10 (1 microg/mouse) for 2 days did not affect inflammation but accelerated bacterial dissemination to the bloodstream. Of mice treated with 1 ip 20 mg/kg Ctri injection, 40% developed septicemia, and only 52% survived. However, the addition of IL-10 to Ctri enhanced bacterial clearance, prevented septicemia, and yielded a 95% survival rate (P<.001). This approach also significantly (P<.05) decreased IL-1beta, IL-6, macrophage inflammatory protein-2, and myeloperoxidase levels in lungs and the production of nitric oxide in bronchoalveolar lavage fluid. Furthermore, Ctri plus IL-10 significantly (P<.05) reduced pulmonary vascular leakage and the appearance of red blood cells in alveoli. These data indicate a beneficial role for IL-10 as an adjunctive therapy to antibiotics against pneumococcal pneumonia.

Topics: Animals; Capillary Permeability; Ceftriaxone; Chemokines; Cytokines; Female; Inflammation; Interleukin-10; Lung; Mice; Pneumonia, Pneumococcal; Pulmonary Circulation; Sepsis; Survival Rate

The inflammatory response following initiation of antibiotic therapy and parameters of neuronal damage were compared during intravenous treatment with quinupristin/dalfopristin (100 mg/kg as either a short or a continuous infusion) and ceftriaxone (10 mg/kg/h) in a rabbit model of Streptococcus pneumoniae meningitis. With both modes of administration, quinupristin/dalfopristin was less bactericidal than ceftriaxone. However, the concentration of proinflammatory cell wall components (lipoteichoic acid (LTA) and teichoic acid (TA)) and the activity of tumour necrosis factor (TNF) in cerebrospinal fluid (CSF) were significantly lower in the two quinupristin/dalfopristin groups than in ceftriaxone-treated rabbits. The median LTA/TA concentrations (25th/75th percentiles) were as follows: (i) 14 h after infection: 133 (72/155) ng/mL for continuous infusion of quinupristin/dalfopristin and 193 (91/308) ng/mL for short duration infusion, compared with 455 (274/2042) ng/mL for ceftriaxone (P = 0.002 and 0.02 respectively); (ii) 17 h after infection: 116 (60/368) ng/mL for continuous infusion of quinupristin/dalfopristin and 117 (41/247) ng/mL for short duration infusion, compared with 694 (156/2173) ng/mL for ceftriaxone (P = 0.04 and 0.03 respectively). Fourteen hours after infection the median TNF activity (25th/75th percentiles) was 0.2 (0.1/1.9) U/mL for continuous infusion of quinupristin/dalfopristin and 0.1 (0.01/3.5) U/mL for short duration infusion, compared with 30 (4.6/180) U/mL for ceftriaxone (P = 0.02 for each comparison); 17 h after infection the TNF activity was 2.8 (0.2/11) U/mL (continuous infusion of quinupristin/dalfopristin) and 0.1 (0.04/6.1) U/mL (short duration infusion), compared with 48.6 (18/169) U/mL for ceftriaxone (P = 0.002 and 0.001). The concentration of neuron-specific enolase (NSE) 24 h after infection was significantly lower in animals treated with quinupristin/dalfopristin: 4.6 (3.3/5.7) microg/L (continuous infusion) and 3.6 (2.9/4.7) microg/L (short duration infusion) than in those treated with ceftriaxone (17.7 (8.8/78.2) microg/L) (P = 0.03 and 0.009 respectively). In conclusion, antibiotic treatment with quinupristin/dalfopristin attenuated the inflammatory response within the subarachnoid space after initiation of antibiotic therapy. The concentration of NSE in the CSF, taken as a measure of neuronal damage, was lower in quinupristin/dalfopristin-treated rabbits than in ceftriaxone-treated rabbits.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Cerebrospinal Fluid Proteins; Disease Models, Animal; Inflammation; Lactic Acid; Lipopolysaccharides; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Neurons; Phosphopyruvate Hydratase; Rabbits; Streptococcus pneumoniae; Subarachnoid Space; Teichoic Acids; Tumor Necrosis Factor-alpha; Virginiamycin

Orbital pseudotumor, also known as idiopathic orbital inflammation, is defined as a nonspecific, nonneoplastic inflammatory process of the orbit without identifiable local or systemic causes. The disorder, first described by Birch-Hirschfield in 1905, is more prevalent in the adult population than in the pediatric population. In our study we discuss two cases of pseudotumor of the orbit in children less than 18 months old. This report will highlight the evaluation and management of pediatric orbital pseudotumor and the importance of its inclusion in the differential diagnosis of orbital disorders in young children.

Topics: Anti-Inflammatory Agents; Ceftriaxone; Cephalosporins; Diagnosis, Differential; Female; Humans; Infant; Inflammation; Male; Methylprednisolone; Orbit; Orbital Diseases; Prednisone; Tomography, X-Ray Computed

The authors report three cases of acute epiploitis diagnosed intraoperatively and discuss the etiopathogenetic hypotheses. They suggest a relationship between acute epiploitis and mesenteric lymphadenitis, as well as their common origin.

Topics: Adolescent; Aged; Cefotaxime; Ceftriaxone; Child; Female; Humans; Inflammation; Mesenteric Lymphadenitis; Omentum; Peritoneal Diseases; Premedication

The role of cytokines in the regulation of articular inflammation and cartilage degradation was evaluated in the rabbit model of Haemophilus influenzae type b arthritis. At 6 and 12 h after intraarticular infection, treatment with IB4 monoclonal antibody to the CD18 leukocyte receptor alone or in combination with dexamethasone resulted in significant reduction of synovial fluid (SF) neutrophil concentration. Treatment with dexamethasone alone was associated with lower SF concentrations of interleukin-1 (IL-1), tumor necrosis factor-alpha, and stromelysin than in other groups. At 24 h after infection, increased cartilage degradation was detected in untreated controls and in animals treated with IB4 alone or in combination with dexamethasone compared with those treated with dexamethasone alone. Multiple regression analyses indicated SF concentration of IL-1 and stromelysin as the significant predictors of cartilage degradation. These data suggest that IL-1 mediates cartilage degradation by regulation of metalloproteinases, such as stromelysin, during acute experimental bacterial arthritis.

Topics: Animals; Antibodies, Monoclonal; Antigens, CD; Arthritis, Infectious; Cartilage, Articular; CD18 Antigens; Ceftriaxone; Cytokines; Dexamethasone; Haemophilus Infections; Haemophilus influenzae; Inflammation; Injections, Intra-Articular; Interleukin-1; Male; Matrix Metalloproteinase 3; Metalloendopeptidases; Neutrophils; Proteoglycans; Rabbits; Regression Analysis; Synovial Fluid; Synovial Membrane; Tumor Necrosis Factor-alpha

Acute uvulitis in adults is a rare condition, especially when associated with acute epiglottitis. Watchful monitoring of the airway, usually in the intensive care unit, is recommended. Along with appropriate antibiotics and steroids, we recommend all patients with acute uvulitis have a lateral radiograph of the neck to rule out acute epiglottitis. To avoid a possible fatality, a high index of suspicion should be maintained at all times in order to appropriately diagnose and treat these patients.

Topics: Ceftriaxone; Dexamethasone; Epiglottitis; Epinephrine; Humans; Inflammation; Male; Middle Aged; Radiography; Uvula

A 9-year-old boy had iridocyclitis and papillitis. Laboratory evaluation revealed a positive Lyme titer. Institution of therapy with intravenous ceftriaxone resulted in regression of the ocular inflammation. Ophthalmologists should consider Lyme disease in the differential diagnosis of iridocyclitis in conjunction with papillitis.

Topics: Ceftriaxone; Child; Follow-Up Studies; Fundus Oculi; Humans; Inflammation; Iritis; Lyme Disease; Male; Optic Disk