Ceftriaxone Treatment Research Articles

Effects of waterpipe tobacco smoke and ceftriaxone treatment on the expression of endocannabinoid receptors in mesocorticolimbic brain regions

Chronic tobacco exposure can alter the endocannabinoid (eCB) system, consequently leading to an anxiety state. In this study, we investigated the effects of waterpipe tobacco smoke (WTS) on cannabinoid receptor 1 and 2 (CBR1 and CBR2) gene and protein expression in mesocorticolimbic brain regions. Using elevated plus maze (EPM) and open field (OF) tests, the effects of WTS exposure on withdrawal-induced anxiety-like behavior were examined. The effect of ceftriaxone (CEF), a β-lactam known to upregulate glutamate transporter 1 (GLT-1), on anxiety and the expression of cannabinoid receptors was also determined. Male Sprague-Dawley rats were randomly assigned to four groups: 1) the Control group was exposed only to standard room air; 2) the WTS group was exposed to tobacco smoke and treated with saline vehicle; 3) the WTS-CEF group was exposed to WTS and treated with ceftriaxone; and 4) the CEF group was exposed only to standard room air and treated with ceftriaxone. Rats were exposed to WTS (or room air) for two hours per day, five days per week for a period of four weeks. Behavioral tests (EPM and OF) were conducted weekly during acute withdrawal, 24 h following WTS exposure. Rats were given either saline or ceftriaxone (200 mg/kg i.p.) for five days during Week 4, 30 min prior to WTS exposure. Withdrawal-induced anxiety was induced by WTS exposure but was reduced by ceftriaxone treatment. WTS exposure decreased CBR1 mRNA and protein expression in the NAc and VTA, but not PFC, and ceftriaxone treatment attenuated these effects. WTS exposure did not change CBR2 mRNA expression in the NAc, VTA, or PFC. These findings demonstrate that WTS exposure dysregulated the endocannabinoid system and increased anxiety-like behavior, and these effects were reversed by ceftriaxone treatment, which suggest the involvement of glutamate transporter 1 in these effects.

Management of Neisseria gonorrhoeae in the United States: Summary of Evidence From the Development of the 2020 Gonorrhea Treatment Recommendations and the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Treatment Guidelines.

Neisseria gonorrhoeae has developed resistance to all first-line recommended therapies, making gonococcal antimicrobial resistance a major public health concern given limited antibiotic options currently and an even smaller antimicrobial development pipeline. Since the release of the Centers for Disease Control and Prevention (CDC) 2015 STD Treatment Guidelines, azithromycin, part of the 2015 dual-drug treatment regimen, has had a rapid rise in resistance. The 2020 CDC Gonorrhea Treatment Recommendations and the 2021 Sexually Transmitted Infections (STI) Treatment Guidelines were developed weighing the priorities of treating the individual, protecting the population, and preventing antimicrobial resistance. Gonorrhea subject matter experts (SME) generated 8 key questions and conducted a literature review of updated data from 2013 to 2019 on gonorrhea antimicrobial resistance, treatment failures, clinical trials, and other key topics. More than 2200 abstracts were assessed, and 248 clinically relevant articles were thoroughly reviewed. SMEs also evaluated N gonorrhoeae antimicrobial resistance data from the Gonococcal Isolate Surveillance Project (GISP). Although there have been reports of ceftriaxone treatment failures internationally, GISP data suggest that ceftriaxone minimal inhibitory concentrations (MICs) have remained stable in the United States, with < 0.1% exhibiting an "alert value" MIC (> 0.25 mcg/mL). However, GISP documented a rapid rise in the proportion of isolates with an elevated MIC (≥ 2.0 mcg/mL) to azithromycin-nearly 5% in 2018. At the same time, new pharmacokinetic/pharmacodynamic data are available, and there is greater recognition of the need for antimicrobial stewardship. The 2021 CDC STI Treatment Guidelines now recommend 500mg ceftriaxone intramuscularly once for the treatment of uncomplicated gonorrhea at all anatomic sites. If coinfection with chlamydia has not been excluded, cotreatment with doxycycline 100mg twice daily for 7 days should be added. Few alternative therapies exist for persons with cephalosporin allergies; there are no recommended alternative therapies for N gonorrhoeae infection of the throat.

Markedly Increasing Antibiotic Resistance and Dual Treatment of Neisseria gonorrhoeae Isolates in Guangdong, China, from 2013 to 2020.

The emergence of multidrug resistance in Neisseria gonorrhoeae is concerning, especially the cooccurrence of azithromycin resistance and decreased susceptibility to extended-spectrum cephalosporin. This study aimed to confirm the antibiotic resistance trends and provide a solution for N. gonorrhoeae treatment in Guangdong, China. A total of 5,808 strains were collected for assessment of antibiotic MICs. High resistance to penicillin (53.80 to 82%), tetracycline (88.30 to 100%), ciprofloxacin (96 to 99.8%), cefixime (6.81 to 46%), and azithromycin (8.60 to 20.03%) was observed. Remarkably, spectinomycin and ceftriaxone seemed to be the effective choices, with resistance rates of 0 to 7.63% and 2.00 to 16.18%, respectively. Moreover, the rates of azithromycin resistance combined with decreased susceptibility to ceftriaxone and cefixime reached 9.28% and 8.64%, respectively. Furthermore, genotyping identified NG-STAR-ST501, NG-MAST-ST2268, and MLST-ST7363 as the sequence types among representative multidrug-resistant isolates. Evolutionary analysis showed that FC428-related clones have spread to Guangdong, China, which might be a cause of the rapid increase in extended-spectrum cephalosporin resistance currently. Among these strains, the prevalence of N. gonorrhoeae was extremely high, and single-dose ceftriaxone treatment might be a challenge in the future. To partially relieve the treatment pressure, a susceptibility test for susceptibility to azithromycin plus extended-spectrum cephalosporin dual therapy was performed. The results showed that all the representative isolates could be effectively killed with the coadministration of less than 1 mg/liter azithromycin and 0.125 mg/liter extended-spectrum cephalosporin, with a synergistic effect according to a fractional inhibitory concentration (FIC) of <0.5. In conclusion, dual therapy might be a powerful measure to treat refractory N. gonorrhoeae in the context of increasing antibiotic resistance in Guangdong, China.

Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague.

Plague pandemics and outbreaks have killed millions of people during the history of humankind. The disease, caused by the bacteria Yersinia pestis, is currently treated effectively with antibiotics. However, in the case of multidrug-resistant (MDR) bacteria, alternative treatments are required. Bacteriophage (phage) therapy has shown efficient antibacterial activity in various experimental animal models and in human patients infected with different MDR pathogens. Here, we evaluated the efficiency of фA1122 and PST phage therapy, alone or in combination with second-line antibiotics, using a well-established mouse model of pneumonic plague. Phage treatment significantly delayed mortality and limited bacterial proliferation in the lungs. However, the treatment did not prevent bacteremia, suggesting that phage efficiency may decrease in the circulation. Indeed, in vitro phage proliferation assays indicated that blood exerts inhibitory effects on lytic activity, which may be the major cause of treatment inefficiency. Combining phage therapy and second-line ceftriaxone treatment, which are individually insufficient, provided protection that led to the survival of all infected animals—a synergistic protective effect that represents a proof of concept for efficient combinatorial therapy in an emergency event of a plague outbreak involving MDR Y. pestis strains.

The incidence of biliary sludge in first trimester pregnancies with hyperemesis gravidarum and its effect on the course of hyperemesis gravidarum

Pregnancy is one of the risk factors for biliary sludge (BS) formation. In this cross-sectional study, a total of 959 pregnant women were included. Serum aspartate aminotransferase, alanine aminotransferase, sodium, potassium, triglycerides, cholesterol levels and the presence of ketones in urine were determined. The presence of BS was investigated using maternal abdominal ultrasound. The incidence of BS in pregnancies complicated by hyperemesis gravidarum (HG) was 14%. The degree of ketonuria and low birth weight were statistically higher in pregnancies with maternal BS than women without sludge. Total weight gain during pregnancies with BS was statistically lower than controls. The incidence of BS in pregnancies with HG does not appear to increase due to HG-related complications, such as dehydration, starvation and weight loss. However, the severity of HG may be worse when HG is associated with sludge. Impact Statement What is already known on this subject? The incidence of biliary sludge (BS) in pregnant women ranges between 10.9% and 36%. Some clinical conditions, such as pregnancy, prolonged fasting, total parenteral nutrition, rapid weight loss and ceftriaxone treatment can play a role in the formation of gallbladder sludge. What do the results of this study add? This is the first study to investigate the incidence of BS in hyperemesis gravidarum (HG) pregnancies. Results show that HG may transiently be associated with BS. HG is more likely to cause a transient increase in new sludge formation. The symptoms and complications related to HG may be more severe when HG is associated with BS. What are the implications of these findings for clinical practice and/or further research? Our study showed that BS can be found in HG patients, and HG can be a predisposing factor for new sludge formation, although this association is generally driven by advanced maternal age and increased baseline serum lipid and alanine aminotransferase levels. BS may also be independently associated with an increased risk of subsequent preterm delivery in women with HG.

Antibiofilm Activity of β-Lactam/β-Lactamase Inhibitor Combination against Multidrug-Resistant Salmonella Typhimurium.

This study was designed to assess the effect of β-lactam/β-lactamase inhibitor combinations on the inhibition of biofilm formation of Salmonella Typhimurium. The anti-planktonic and anti-biofilm activities of ampicillin (AMP), ceftriaxone (CEF), and combination treatments of antibiotics and sulbactam (AMP + SUL and CEF + SUL) were evaluated against antibiotic-sensitive S. Typhimurium ATCC 19585 (STAS) and clinically isolated multidrug-resistant (MDR) S. Typhimurium CCARM 8009 (STMDR). Compared to the control, the minimum inhibitory concentrations (MICs) of AMP against STAS and CEF against STMDR were decreased from 32 to 16 μg/mL and 0.25 to 0.125 μg/mL, respectively, in the presence of SUL. The numbers of STMDR treated with AMP + SUL and CEF + SUL were effectively reduced by more than 2 logs after 4 h of incubation at 37 °C. The β-lactamase activities of STAS and STMDR treated with AMP and CEF were reduced from 3.3 to 2.6 μmol/min/mL and from 8.3 to 3.4 μmol/min/mL, respectively, in the presence of SUL. The biofilm cell numbers of STAS and STMDR were reduced at all treatments after 24 h of incubation at 37 °C. The biofilm cell numbers of STAS and STMDR were reduced by more than 2 logs in the presence of SUL compared to the AMP and CEF alone. The lowest relative fitness level was 0.6 in STAS treated with AMP + SUL, while no significant differences in the relative fitness were observed in STMDR. This study suggests that β-lactamase inhibitors (BLIs) could be used for controlling biofilm formation of β-lactamase-producing multidrug-resistant S. Typhimurium.

Pneumococcal meningitis and COVID-19: dangerous coexistence. A case report

BackgroundSARS-CoV-2 is the major cause of infections in humans since December 2019 and is top of the global health concern currently. Streptococcus pneumoniae is one of the leading pathogens of invasive bacterial diseases, including pneumonia, sepsis, and meningitis. Moreover, this bacteria is mostly responsible for secondary infections subsequent to post-viral respiratory disease. Co-infections with bacterial and viral pathogens are associated with severe course of the disease and are a major cause of mortality. In this report, we describe a rare case of COVID-19 patient with pneumococcal sepsis and meningitis of unsuccessful course.Case presentationA 89-year-old man, not vaccinated against SARS-CoV-2 infection, was diagnosed with COVID-19 pneumonia. Patient required oxygen therapy due to respiratory failure. The initial treatment of viral infection with tocilizumab and dexamethasone allowed for the stabilization of the patient’s condition and improvement of laboratory parameters. On the 9th day of hospitalization the patient’s condition deteriorated. Consciousness disorders and acute respiratory disorders requiring intubation and mechanical ventilation were observed. Brain computed tomography excluded intracranial bleeding. The Streptococcus pneumoniae sepsis with concomitant pneumoniae and meningitis was diagnosed based on microbiological culture of blood, bronchial wash, and cerebrospinal fluid examination. Despite targeted antibiotic therapy with ceftriaxone and multidisciplinary treatment, symptoms of multiple organ failure increased. On the 13th day of hospitalization, the patient died.ConclusionsCo-infections with bacterial pathogens appear to be not common among COVID-19 patients, but may cause a sudden deterioration of the general condition. Not only vascular neurological complications, but also meningitis should be always considered in patients with sudden disturbances of consciousness. Anti-inflammatory treatment with the combination of corticosteroids and tocilizumab (or tocilizumab alone) pose a severe risk for secondary lethal bacterial or fungal infections. Thus, treating a high-risk population (i.e. elderly and old patients) with these anti-inflammatory agents, require daily clinical assessment, regular monitoring of C-reactive protein and procalcitonin, as well as standard culture of blood, urine and sputum in order to detect concomitant infections, as rapidly as possible.

Synbiotic supplementation and oxalate homeostasis in rats: focus on microbiota oxalate-degrading activity

The present study aimed (i) to evaluate whether ceftriaxone treatment could affect not only intestinal oxalate-degrading bacteria number but also their total activity to degrade oxalate and influence oxalate homeostasis in rats, (ii) and to estimate the ability of commercially available inulin-contained synbiotic to restore fecal oxalate-degrading activity and ceftriaxone-induced disruption of oxalate homeostasis in rats. Twenty-eight female Wistar rats (200-300g) were randomly divided into four groups (n = 7). Group 1 was treated with vehicle sterile water (0.1ml, i.m., 14days); Group 2 received synbiotic (30mg/kg, per os, 14days); Group 3 was treated with ceftriaxone (300mg/kg, i.m., 7days); Group 4 was supplemented with ceftriaxone and synbiotic. Oxalate-degrading bacteria number and their total activity, urinary and plasma oxalate concentrations were measured on days 1 and 57 after the treatment withdrawal. The redoximetric titration with KMnO4 was adopted to evaluate the total oxalate-degrading activity in highly selective Oxalate Medium. Ceftriaxone treatment reduced total fecal oxalate-degrading activity independently on oxalate-degrading bacteria number and increased urinary and plasma oxalate concentrations. The synbiotic had higher oxalate-degrading activity vs probiotics and was able to restore fecal oxalate-degrading activity and significantly decrease urinary oxalate excretion in antibiotic-treated rats. Total fecal oxalate-degrading activity but not oxalate-degrading bacteria number should be thoroughly examined in the future to develop predictive diagnostics methods, targeted prevention and personalized treatment in kidney stone disease. Synbiotic supplementation had a beneficial effect on the total oxalate-degrading activity of gut microbiota, which resulted in decreased UOx excretion in rats.

An unusual presentation of scrub typhus in a child: a case report

BackgroundScrub Typhus (ST) is an acute, febrile zoonotic disease caused by the bacterium Orientia tsutsugamushi which is endemic to the Asia-Pacific region. Infected adults rarely present with sensorineural hearing loss and otalgia. Though few cases of pediatric cases are known to present with otalgia, no pediatric cases of sensorineural deafness complicating ST have been reported to date.Case presentationA 5-year-old, previously healthy girl presented with a one-week history of high-grade intermittent fever, Headache and right ear pain with a recent onset of reduced hearing. She had a fever up to 39 °C, cervical lymphadenopathy, bilateral pleural effusion with diffuse infiltrations, and mild hepatosplenomegaly with no evidence of rash. Her initial examination was normal except for mildly enlarged tonsils. Unilateral right ear hearing loss was noted using Weber’s test. Evidence of progressive, mild anemia, and raised inflammatory markers was noted. Diagnosis of scrub typhus was confirmed by positive detection of Orentia tsutsugamushi IgM antibodies on rapid diagnostic test and the presence of chigger mite in the right external auditory canal on repeat examination. She responded dramatically to the empirical treatment of ceftriaxone and doxycycline. On follow-up, she did not have any residual hearing loss and her ear pain had resolved completely.ConclusionAcute onset hearing loss or severe otalgia with or without findings should be an important diagnostic clue for suspecting scrub typhus in patients who present with a history of fever especially in endemic areas.

Risk Factors for Severity and Mortality in Adult Patients Confirmed with COVID-19 in Sierra Leone: A Retrospective Study.

Background:The coronavirus disease 2019 (COVID-19) is a highly infectious respiratory disease. There is no recommended antiviral treatment approved for COVID-19 in Sierra Leone, and supportive care and protection of vital organ function are performed for the patients. This study summarized the clinical characteristics, drug treatments, and risk factors for the severity and prognosis of COVID-19 in Sierra Leone to provide evidence for the treatment of COVID-19.Methods:Data of 180 adult COVID-19 patients from the 34th Military Hospital in Freetown Sierra Leone between March 31, 2020 and August 11, 2020 were retrospectively collected. Patients with severe and critically ill are classified in the severe group, while patients that presented asymptomatic, mild, and moderate disease were grouped in the non-severe group. The clinical and laboratory information was retrospectively collected to assess the risk factors and treatment strategies for severe COVID-19. Demographic information, travel history, clinical symptoms and signs, laboratory detection results, chest examination findings, therapeutics, and clinical outcomes were collected from each case file. Multivariate logistic analysis was adopted to identify the risk factors for deaths. Additionally, the clinical efficacy of dexamethasone treatment was investigated.Results:Seventy-six (42.22%) cases were confirmed with severe COVID-19, while 104 patients (57.78%) were divided into the non-severe group. Fever (56.67%, 102/180) and cough (50.00%, 90/180) were the common symptoms of COVID-19. The death rate was 18.89% (34/180), and severe pneumonia (44.12%, 15/34) and septic shock (23.53%, 8/34) represented the leading reasons for deaths. The older age population, a combination of hypertension and diabetes, the presence of pneumonia, and high levels of inflammatory markers were significantly associated with severity of COVID-19 development (P < 0.05 for all). Altered level of consciousness [odds ratio (OR) = 56.574, 95% confidence interval (CI) 5.645–566.940, P = 0.001], high levels of neutrophils (OR = 1.341, 95%CI 1.109–1.621, P = 0.002) and C-reactive protein (CRP) (OR = 1.014, 95%CI 1.003–1.025, P = 0.016) might be indicators for COVID-19 deaths. Dexamethasone treatment could reduce mortality [30.36% (17/56) vs. 50.00% (10/20)] among severe COVID-19 cases, but the results were not statistically significant (P > 0.05).Conclusions:The development and prognosis of COVID-19 may be significantly correlated with consciousness status, and the levels of neutrophils and CRP.

Choroidal neovascularization secondary to ocular syphilis

Choroidal neovascularization (CNV) is a very rare but sight-threatening complication of ocular syphilis. We reported the case of a 51-year-old woman who presented with a 2-week history of visual loss in the right eye (RE). Fundus examination demonstrated vitritis and the optic disc margin blurring. Fundus fluorescein angiography (FFA) showed the presence of optic nerve edema, macular edema, and diffused impairment of the blood-retinal barrier with leakage areas, which led to the diagnosis of bilateral neuroretinitis. Optical coherence tomography (OCT) of the right macula evidenced irregularities of the retinal pigment epithelium (RPE), subretinal fluid and hyperreflective material. Besides, workup indicated positive serology for syphilis and the patient received combined treatment of ceftriaxone, systemic and topical steroids as well as cycloplegic medications. The woman did not consent to lumbar puncture or intravitreal anti-vascular epithelial growth factor (anti-VEGF) injection, therefore the prognosis for improvement of visual acuity is poor.Abbreviations: anti-VEGF = anti-vascular epithelial growth factor, AMD = age related macular degeneration, BCVA = best corrected visual acuity, CNS = central nervous system, CNV = choroidal neovascularization, CSF = cerebrospinal fluid, FFA = fundus fluorescein angiography, FTA-ABS = fluorescent treponemal antibody absorption, HIV = human immunodeficiency virus, iCNV = inflammatory CNV, IOP = intraocular pressure, LE = left eye, MRI = magnetic resonance imaging, OCT = optical coherence tomography, OCTA = optical coherence tomography angiography, RE = right eye, RPE = retinal pigment epithelium, RPR = rapid plasma regain, TP-PA = Treponema pallidum particle agglutination, VDRL = Venereal Disease Research Laboratory

682. Implantable Cardioverter-Defibrillator Lead Vegetation with Long-Standing Actinomyces neuii Bacteremia

BackgroundEndocarditis caused by Actinomyces species is uncommon with only 30 cases reported in contemporary literature. MethodsWe present a novel case of cardiovascular implantable electronic device (CIED) endocarditis secondary to infection by Actinomyces neuii – a unique non-branching member of the species that grows in both anaerobic and aerobic media.ResultsOur patient, a 51-year-old female, with a history of implantable cardioverter-defibrillator (ICD) placement 17 years prior for heart failure, presented with six weeks of fevers and rigors. She was referred to the infectious disease clinic for evaluation of pyrexia of unknown origin. Her examination was unremarkable, and the ICD pocket was uninflamed. Her initial labs revealed mildly elevated inflammatory markers and renal insufficiency. Blood cultures were positive for slow-growing non-branching gram-positive rods in both aerobic and anaerobic media. These were identified as Actinomyces neuii by mass spectrometry. Review of outside records showed positive blood cultures with Actinomyces neuii at another facility two weeks prior to our evaluation which were not acted upon and thought to be bacterial contamination. The patient was further evaluated with a transesophageal echocardiogram that demonstrated a 3.3 x 2.2cm mobile vegetation attached to the ICD lead. She subsequently underwent removal of her Saint Jude cardiac resynchronization therapy defibrillator and leads using laser and snaring techniques, but the tail end of the ventricular lead fractured and could not be retrieved. The ICD pocket was also found to be infected. A planned 6-week course of IV ampicillin was interrupted by 2 weeks of ceftriaxone for treatment of an intercurrent lower respiratory tract infection. The patient regained her baseline health and was discharged 2 weeks after ICD removal with a LifeVest. She is to complete 12 months of oral amoxicillin therapy after completion of IV antibiotics in view of retained lead fragment, and long standing Actinomyces bacteremia - consistent with published management strategies. Figure 1. Transesophageal echocardiogram demonstrating size of vegetation. Figure 2. Three-dimensional view demonstrating vegetation on the ICD lead.ConclusionHere we describe the first known case of Actinomyces neuii CIED endocarditis with a large lead vegetation and long-standing bacteremia, presenting as pyrexia of unknown origin.Disclosures All Authors: No reported disclosures

AAUS guidelines 2021 revision sexually transmitted infection (STIs) diagnostic strategy for STI

AAUS guidelines 2021 revision sexually transmitted infection (STIs) diagnostic strategy for STI

Neuroprotective Effects of Ceftriaxone Involve the Reduction of Aβ Burden and Neuroinflammatory Response in a Mouse Model of Alzheimer's Disease.

Ceftriaxone (CEF) is a safe and multipotent antimicrobial agent that possesses neuroprotective properties. Earlier, we revealed the restoration of cognitive function in OXYS rats with signs of Alzheimer’s disease (AD)-like pathology by CEF along with its modulating the expression of genes related to the system of amyloid beta (Aβ) metabolism in the brain. The aim of this study was to determine the effects of CEF on behavior, Aβ deposition, and associated neuroinflammation using another model of an early AD-like pathology induced by Aβ. Mice were injected bilaterally i.c.v. with Aβ fragment 25–35 to produce the AD model, while the CEF treatment (100 mg/kg/day, i.p., 36 days) started the next day after the surgery. The open field test, T-maze, Barnes test, IntelliCage, and passive avoidance test were used for behavioral phenotyping. Neuronal density, amyloid accumulation, and the expression of neuroinflammatory markers were measured in the frontal cortex and hippocampus. CEF exhibited beneficial effects on some cognitive features impaired by Aβ neurotoxicity including complete restoration of the fear-induced memory and learning in the passive avoidance test and improved place learning in the IntelliCage. CEF significantly attenuated amyloid deposition and neuroinflammatory response. Thus, CEF could be positioned as a potent multipurpose drug as it simultaneously targets proteostasis network and neuroinflammation, as well as glutamate excitotoxicity, oxidative pathways, and neurotrophic function as reported earlier. Together with previous reports on the positive effects of CEF in AD models, the results confirm the potential of CEF as a promising treatment against cognitive decline from the early stages of AD progression.

Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats.

Disrupted glutamate clearance in the synaptic cleft leads to synaptic dysfunction and neurological diseases. Decreased glutamate removal from the synaptic cleft is known to cause excitotoxicity. Data on the physiological effects of increased glutamate clearance are contradictory. This study investigated the consequences of ceftriaxone (CTX), an enhancer of glutamate transporter 1 expression, treatment on long-term synaptic potentiation (LTP) in the hippocampus of young rats. In this study, 5-day administration of CTX (200 mg/kg) significantly weakened LTP in CA3-CA1 synapses. As shown by electrophysiological recordings, LTP attenuation was associated with weakening of N-Methyl-D-aspartate receptor (NMDAR)-dependent signaling in synapses. However, PCR analysis did not show downregulation of NMDAR subunits or changes in the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits. We assume that extracellular burst stimulation activates fewer synapses in CTX-treated animals because increased glutamate reuptake results in reduced spillover, and neighboring synapses do not participate in neurotransmission. Attenuation of LTP was not accompanied by noticeable behavioral changes in the CTX group, with no behavioral abnormalities observed in the open field test or Morris water maze test. Thus, our experiments show that increased glutamate clearance can impair long-term synaptic plasticity and that this phenomenon can be considered a potential side effect of CTX treatment.

In vivo Analysis of the Resistance of the Meshes to Escherichia coli Infection.

Background: The mesh infection is mostly related to the gram-negative bacteria, such as Escherichia coli (E. coli) for emergency surgery of incarcerated hernia. However, few study investigated the effects of E. coli concentration, mesh materials and antibiotic prophylaxis on mesh infection after hernioplasty. The aim of this study was to evaluate the bacterial resistance to E. coli for three different materials of mesh, and to measure the minimum E. coli concentration for mesh infection with and without antibiotic prophylaxis in a rat model.Methods: Three types of mesh (polytetrafluoroethylene, polypropylene, and biologic meshes) were used in the repair of an acute ventral hernia rat model in the setting of different concentrations of E. coli loads and antibiotics. At the 8th day after surgery, mesh samples were sent for microbiologic and histologic analyses.Results: The positive rates of bacterial culture increased with E. coli concentration. The biologic mesh showed better bacterial resistance compared to polytetrafluoroethylene mesh and polypropylene mesh when the concentration of E. coli ranges from 106 CFU/ml to 108 CFU/ml (P = 0.002 and P = 0.029, respectively). Prophylactical ceftriaxone treatment could not decrease the colonization rate of E. coli at 106 CFU/ml or 108 CFU/ml in each group (P > 0.05). The scores of neovascularization in polypropylene mesh and biologic mesh were similar, which was higher than that of polytetrafluoroethylene mesh (P < 0.05). Compared with other meshes, biologic mesh showed better tolerance to 106 CFU/ml E. coli with respect to inflammation, depth of inflammation, neovascularization, cellular repopulation and foreign body giant cells.Conclusion: The biologic mesh had better E. coli resistance compared to polytetrafluoroethylene mesh and polypropylene mesh when the E. coli concentration is higher than 106 CFU/ml in rats. Antibiotic prophylaxis was useful when the contamination was not particularly severe.

Ceftriaxone regulates glutamate production and vesicular assembly in presynaptic terminals through GLT-1 in APP/PS1 mice

Perturbations in the glutamate–glutamine cycle and glutamate release from presynaptic terminals have been involved in the development of cognitive deficits in Alzheimer’s disease (AD) patients and mouse models. Glutamate transporter-1 (GLT-1) removes glutamate from the synaptic cleft and transports it into astrocytes, where it is used as substrate for the glutamate–glutamine cycle. Ceftriaxone has been reported to improve cognitive deficits in AD mice by increasing GLT-1 expression, glutamate transformation to glutamine, and glutamine efflux from astrocytes. However, the impact of ceftriaxone on glutamine metabolism in neurons is unknown. The present study aimed to investigate whether ceftriaxone regulated the production and vesicular assembly of glutamate in the presynaptic terminals of neurons and to determine GLT-1 involvement in this process. We used the amyloid precursor protein (APP)/presenilin-1 (PS1) AD mouse model and GLT-1 knockdown APP/PS1 (GLT-1+/−/APP/PS1) mice. The expression levels of sodium-coupled neutral amino-acid transporter 1 (SNAT1) and vesicular glutamate transporters 1 and 2 (VGLUT1/2) were analyzed by immunofluorescence and immunohistochemistry staining as well as by Western blotting. Glutaminase activity was assayed by fluorometry. Ceftriaxone treatment significantly increased SNAT1 expression and glutaminase activity in neurons in APP/PS1 mice. Similarly, VGLUT1/2 levels were increased in the presynaptic terminals of APP/PS1 mice treated with ceftriaxone. The deletion of one GLT-1 allele in APP/PS1 mice prevented the ceftriaxone-induced upregulation of SNAT1 and VGLUT1/2 expression, indicating that GLT-1 played an important role in ceftriaxone effect. Based on the role of SNAT1, glutaminase, and VGLUT1/2 in the glutamate–glutamine cycle in neurons, the present results suggested that ceftriaxone improved the production and vesicular assembly of glutamate as a neurotransmitter in presynaptic terminals by acting on GLT-1 in APP/PS1 mice.

Thiosulfinate-Enriched Allium sativum Extract as an Adjunct to Antibiotic Treatment of Sepsis in a Rat Peritonitis Model

Up to now, there are no studies that have shown a decrease in morbidity and mortality in the context of sepsis and septic shock, except for antibiotic therapy and the objective-guided resuscitation strategy. The goal was to evaluate the use of thiosulfinate-enriched Allium sativum extract (TASE) as an adjuvant in the management of sepsis. An experimental in vivo study was carried out with male Sprague Dawley® rats. Animals were randomized in three treatment groups: the control group (I), antibiotic (ceftriaxone) treatment group (II) and ceftriaxone plus TASE treatment group (III). All animals were housed and inoculated with 1 × 1010 CFU/15 mL of intraperitoneal Escherichia coli ATCC 25922. Subsequently, they received a daily treatment according to each group for 7 days. Clinical, analytical, microbiological, and histopathological parameters were evaluated. Statistically significant clinical improvement was observed in the ceftriaxone plus TASE vs. ceftriaxone group in weight, ocular secretions, whiskers separation and physical activity level (p ≤ 0.05). When comparing interleukins on the third day of treatment between II and III, we found statistically significant differences in IL-1 levels (p &lt; 0.05). Blood and peritoneal liquid cultures of group I were positive for multisensitive E. coli. Group II and III cultures were negative for E. coli, although an overgrowth of Enterococcus faecalis was found. In conclusion, TASE used as an adjuvant to antibiotic treatment in the management of sepsis could improve response profiles with sepsis attenuation, thus reducing overall mortality after an animal peritonitis model.

Decreases in Reported Sexually Transmitted Infections During the Time of COVID-19 in King County, WA: Decreased Transmission or Screening?

In response to the COVID-19 pandemic, Washington State's Stay Home, Stay Healthy (SHSH) order was implemented on March 24, 2020. We hypothesized that pandemic mitigation measures might reduce sexually transmitted infection (STI) screening and/or transmission. We used King County, WA STI surveillance and sexual health clinic (SHC) data from January 1, 2019, to July 31, 2020. We calculated mean weekly case counts for gonorrhea, primary and secondary (P&S) syphilis, male urethral gonorrhea, and early latent (EL) syphilis for 3 periods in 2020: pre-SHSH (January 1-March 23), SHSH (March 24-June 5), and reopening (June 6-July 31). Primary and secondary syphilis and male urethral gonorrhea were used as proxies for sexual behavior, and EL syphilis was used as a proxy for STI screening. We compared SHC visits (2019 vs. 2020) and SHC gonorrhea treatment practices (across 2020 periods). Compared with January to July 2019, from January to July 2020, reported cases of gonorrhea, male urethral gonorrhea, P&S syphilis, and EL syphilis decreased by 9%, 5%, 16%, and 22%, respectively. Mean weekly case counts of gonorrhea, male urethral gonorrhea, and EL syphilis decreased pre-SHSH to SHSH, but all returned to pre-SHSH levels during reopening. Sexual health clinic visits during SHSH were 55% lower in 2020 than in 2019. In the SHC during SHSH, ceftriaxone treatment of gonorrhea decreased, whereas cefixime/cefpodoxime treatment and gonorrhea treatment with no testing increased. Decreases in reported STIs concurrent with COVID-19 SHSH may reflect a true decline in STI transmission. However, the larger decreases in asymptomatic infections indicate that much of the observed decrease was likely due to decreased screening.

Comparison of Efficacy of Azithromycin Versus Ceftriaxone in Treatment of Enteric Fever

Objective: Research was conducted at the Hayatabad Medical Complex in Peshawar to evaluate the relative effectiveness of azithromycin and ceftriaxone in the treatment of enteric fever. Methods: After the ethical approval from institute review board, this random controlled trial was conducted at Department of Pediatrics, Hayatabad Medical Complex, Peshawar, from 20 July, 2019 to 20 Jan, 2020. Each patient was randomly assigned to a treatment group through toss method in Group A and Group B. Patients in Group A received azithromycin (20 mg/kg/day; maximum, 1000 mg/day) and patients in Group B were administered with ceftriaxone (75 mg/kg/day; maximum, 2.5 g/day). Efficacy of both drugs was determined keeping in view complete resolution of symptoms of enteric fever within a week time. Results: The mean ± S. D of age of the participants in both groups were 5.38±1.95 and 5.74±1.84 years. The mean ± S. D of disease duration of the participants in both groups were 6.14±1.25 and 5.90±1.17 days. The mean ± S. D of time of defersevence of the participants in both groups were 2.38±0.57 and 4.66±0.716. In azithromycin group, 44 (88%) patients showed effective results while in the ceftriaxone group, 23 (46%) patients showed effective results. P Value = 0.000 Conclusion: Azithromycin could be a convenient and cheap alternative for the treatment of typhoid fever, especially in children in our local population. Keywords: Azithromycin, Ceftriaxone, Typhoid Fever