A case of leptospirosis in transcarpathia complicated with Jarisch-Herxheimer reaction.

A case report of Jarisch-Herxheimer (JHR) reaction on a 10th day of Leptospirosis caused by Leptospira Pomona. JHR occurs as a complication of an antibiotic treatment of various spirochetes and may lead to respiratory distress syndrome, renal failure, hepatic insufficiency, and multiple organ failure. This case represents a skin and cardio-vascular form of JHR with no lung involvement. The patient was treated with benzylpenicillin and low dexamethasone doses for 5th day of the disease with a shift to ceftriaxone and high doses of methylprednisolone. The fastest diagnosis of a sporadic zoonotic disease, early start of antibiotic therapy, and adequate doses of corticosteroids are key to the successful treatment of leptospirosis.

Safety of subcutaneous versus intravenous ceftriaxone administration in older patients: A retrospective study.

BACKGROUND: Antibiotics play a central role in infection management. In older patients, antibiotics are frequently administered subcutaneously. Ceftriaxone pharmacokinetics after subcutaneous administration is well documented, but little data are available on its safety. METHODS: We compared the occurrence of adverse events associated with ceftriaxone administered subcutaneously versus intravenously in ≥75-year-old patients. We used data from a single-center, retrospective, clinical-administrative database to compare the occurrence of adverse events at day 14 and outcome at day 21 in older patients who received ceftriaxone via the subcutaneous route or the intravenous route at Rennes University Hospital, France, from May 2020 to February 2023. RESULTS: The subcutaneous and intravenous groups included 402 and 3387 patients, respectively. Patients in the subcutaneous group were older and more likely to receive palliative care. At least one adverse event was reported for 18% and 40% of patients in the subcutaneous and intravenous group, respectively (RR = 2.21). Mortality at day 21 was higher in the subcutaneous route group, which could be linked to between-group differences in clinical and demographic features. CONCLUSIONS: In ≥75-year-old patients, ceftriaxone administered by the subcutaneous route is associated with less-adverse events than by the intravenous route. The subcutaneous route, which is easier to use, has a place in infection management in geriatric settings.

A randomized study of ceftriaxone for the prevention of infections in hospitalized patients with advanced cirrhosis.

BACKGROUND: Infections frequently complicate hospital admission among patients with cirrhosis and are associated with adverse outcomes. In specific settings, administration of prophylactic antibiotics has been shown to improve outcomes. In this pilot study, we aimed to assess the feasibility of a randomized study of whether prophylactic ceftriaxone (CTX), administered to hospitalized patients with advanced cirrhosis (Model for End-Stage Liver Disease-Sodium ≥ 18) without known infection, could reduce the incidence of infection. We also sought to determine whether we could identify patients most likely to benefit through the use of clinical and laboratory parameters. METHODS: Hospitalized patients with cirrhosis, with Model for End-Stage Liver Disease-Sodium ≥ 18 and no known infection after evaluation, were randomly assigned in a double-blinded fashion to receive either CTX 1 gr/day or placebo for up to 7 days. Subjects were monitored for incident infection and other outcomes of interest, including adverse reactions such as the development of C. difficile infection. Biomarkers of interest, including C-reactive protein and procalcitonin, were measured before initiation of treatment. RESULTS: Thirty subjects were enrolled and received CTX or placebo (15 subjects each) per protocol. There were no observed statistically significant differences between groups in incidence of infection, mortality, length of stay, or key laboratory parameters, including C-reactive protein and procalcitonin. Adverse events related to treatment were rare and clinically of minor significance. CONCLUSIONS: Overall, enrollment of subjects proved feasible, and results from this pilot study, while inadequate for confirmation of the potential efficacy of CTX, provide evidence of study feasibility for future, more definitive clinical trials.

Ceftriaxone-induced encephalopathy in a patient with a normal renal function.

Ceftriaxone-induced encephalopathy is an exceptionally rare adverse effect of this commonly used cephalosporin and is generally observed in patients undergoing haemodialysis or suffering from severe renal failure. We present a case of a fit woman in her mid-80s with a normal renal function who developed severe fluctuating neurological symptoms (aphasia, loss of contact, chorea-like tongue movements) while being treated with ceftriaxone for a urinary tract infection with bacteraemia. The symptoms began on day 4 of treatment and an adverse drug reaction was suspected on day 7, after exhaustive investigations failed to reveal another cause. A complete recovery was observed 3 days after discontinuing ceftriaxone. Our case highlights the need to consider the diagnosis of ceftriaxone encephalopathy, even if the traditional risk factors are lacking. In this article, we also provide a brief overview of the pathophysiology as well as a literature review concerning the subject.

Association Between Common Empiric Antibiotic Regimens and Clostridioides Difficile Infection in Pediatric Appendicitis.

BACKGROUND: Clostridioides Difficile Infection (CDI) is a serious antibiotic related complication that has been reported among children undergoing treatment of appendicitis. CDI likelihood amongst different empiric antibiotic regimens for appendicitis remains unclear but likely has important implications for antibiotic stewardship. METHODS: A retrospective cohort study of the Pediatric Health Information System was used to examine patients ages 1 through 18 who received operative management of acute appendicitis. Common empiric antibiotic regimens 1) Ceftriaxone & Metronidazole (CM) 2) Piperacillin & Tazobactam (PT) and 3) Cefoxitin were compared. Study outcomes were CDI within 28 days post-appendectomy and 30-day post-appendectomy percutaneous drainage procedures. Subset analyses were repeated to only include hospitals that standardized empiric antibiotic choice. RESULTS: Of 105,911 patients, 220 (0.21 %) developed CDI. CDI was more common in patients that received CM (CM 0.29 % vs PT 0.15 % vs Cefoxitin 0.18 %; P < 0.01). On adjusted analysis, PT was associated with a lower likelihood of CDI (OR, 0.48; 95%CI, 0.31-0.74) compared to CM which was consistent in hospitals with standardized antibiotic choice. Exposure to more unique antibiotic regimens (OR, 1.70; 95 % CI, 1.50-1.93) and higher total antibiotic days (OR, 1.17; 95 % CI 1.13-1.21) were associated with an increased likelihood of CDI. There was no significant difference in the likelihood of post-appendectomy percutaneous drainage between antibiotic regimens. CONCLUSIONS: CDI is rare following appendectomy for pediatric appendicitis. While PT was associated with statistically lower rates of CDI compared to CM, antibiotic stewardship efforts to avoid mixed regimens and decrease overall antibiotic exposure warrant exploration. LEVEL OF EVIDENCE: Level III.

Ceftriaxone-induced Kounis syndrome: A case report and review of the literature.

Kounis syndrome is defined as cardiovascular symptoms that occur secondary to allergic or hypersensitivity insults, and is also called allergic angina and allergic myocardial infarction. We report a case of pre-operative ceftriaxone-induced Kounis syndrome with no evident dermatological manifestation, and describe our diagnostic dilemma. The patient was symptomatically managed and discharged in stable condition with a warning against future use of ceftriaxone.

Effect of Ceftriaxone Dosage and Albumin-Bilirubin Score on the Risk of Ceftriaxone-Induced Liver Injury.

The albumin-bilirubin (ALBI) score is an index of hepatic functional reserve and is calculated from serum albumin and total bilirubin levels. However, the relationship between ceftriaxone (CTRX)-induced liver injury and ALBI score remains unknown. Therefore, we aimed to elucidate the risk of CTRX-induced liver injury based on the ALBI scores and CTRX dosage. This was a single-center, retrospective, case-control study of 490 patients and the primary outcome was CTRX-induced liver injury. We performed a COX regression analysis using age ≥75 years, male sex, alanine aminotransferase levels, ALBI score, and CTRX dosage regimen (4 ≥2 or 1 g/d) as explanatory factors. We also performed 1 : 1 propensity score matching between non-liver injury and liver injury groups. The incidence of liver injury was 10.0% (49/490). In COX regression analysis, CTRX 4 g/d was an independent risk factor for liver injury (95% coefficient interval: 1.05-6.96, p = 0.04). Meanwhile, ALBI score ≥-1.61 was an independent factor for liver injury (95% coefficient interval: 1.03-3.22, p = 0.04) with the explanatory factor of ≥2 and 1 g/d. The Kaplan-Meier curve indicated that the cumulative risk for CTRX-induced liver injury was significantly higher in the ALBI score ≥-1.61 group than in the ALBI score <-1.61 group before propensity score matching (p = 0.032); however, no significant differences were observed after propensity score matching (p = 0.791). These findings suggest that in patients treated with CTRX with ALBI score ≥-1.61, frequent liver function monitoring should be considered.

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

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

Sudden-onset gallbladder rupture due to Ceftriaxone-associated pseudolithiasis in a patient with acquired hemophilia A.

We herein report a 76-year-old man with acquired hemophilia A (AHA) who developed gallbladder rupture due to Ceftriaxone (CTRX)-associated pseudolithiasis. The patient was admitted for an examination of systemic subcutaneous bleeding. A blood test showed a prolonged activated partial thromboplastin time and sequentially revealed low factor VIII activity (<1%) and a high factor VIII inhibitor level of 143 BU/mL. The patient was thus diagnosed with AHA. After admission, he developed a high-grade fever and was administered intravenous CTRX, considering the possibility of psoas abscess or cellulitis. Although his high-grade fever was improved, computed tomography incidentally showed a high-density lesion in the gallbladder, suggestive of CTRX-associated pseudolithiasis without clinical symptoms. Despite cessation of CTRX, the pseudolithiasis never disappeared, and the patient suddenly died after rapid progression of abdominal bloating. An autopsy revealed that the gallbladder was severely swollen and had ruptured with hemorrhaging because of hemorrhagic cholecystitis, caused by CTRX-associated pseudolithiasis with AHA. Our case demonstrated that CTRX-associated pseudocholelithiasis can unexpectedly induce gallbladder hemorrhaging and rupture in a patient with a bleeding diathesis, including AHA. CTRX-associated pseudocholelithiasis can cause a fatal outcome in patients with a bleeding disorder, even if CTRX is ceased as soon as pseudocholelithiasis is detected.

Ceftriaxone-associated Biliary Pseudolithiasis with Elderly Type 1 Diabetes Mellitus: Two Case Reports.

Biliary pseudolithiasis is a ceftriaxone (CTRX)-induced complication, but the risk in cases of elderly type 1 diabetes mellitus (T1DM) is unclear. Case 1: A 78-year-old woman with T1DM complicated by diabetic autonomic neuropathy was admitted with pneumonia and treated with CTRX. On day 8, biliary pseudolithiasis and cholecystitis were observed. Case 2: an 80-year-old woman with T1DM was suspected of having a urinary tract infection and treated with CTRX. After a week, she developed asymptomatic biliary pseudolithiasis with gastroparesis. CTRX-associated biliary pseudolithiasis was thus noted in these cases of elderly T1DM. CTRX should be cautiously administered, especially in elderly T1DM patients with diabetic autonomic neuropathy.

Evaluation of the tolerance of ceftriaxone by subcutaneous route in patients ≥75 years old in geriatric departments: a prospective observational study.

OBJECTIVES: The subcutaneous (SC) route provides an alternative to the IV or oral route for drug administration in the elderly. The benefits of SC administration have been proven for hydration but are still debated for antibiotics because tolerance remains uncertain, especially in the frail geriatric population. Here, we aimed to improve current knowledge concerning the tolerance profile of ceftriaxone SC administration at both the systemic and cutaneous level, as well as in terms of pain. PATIENTS AND METHODS: This was a prospective descriptive study of SC ceftriaxone tolerance in a geriatric department. We included all patients over 75 years of age who received a prescription for SC ceftriaxone in our hospital over a 5 month period. METHODS: We evaluated the systemic and local tolerance of SC ceftriaxone. Nurses were asked about their perceptions concerning its use. RESULTS: Among 117 patients, 57% presented with pain and 60% with a mild local adverse effect, such as the formation of oedema in one-third of patients, induration or transient erythema. Finally, there were no serious local adverse effects and two systemic adverse effects were observed (one diarrhoea and one Clostridioides difficile colitis). Pain was mainly related to the skin breach and oedema formation. CONCLUSIONS: We did not find any worrying signs concerning the use of SC ceftriaxone but this study shows that its wide use must consider pain management, which is often overlooked.

Risk Factors for Ceftriaxone-Associated Pseudolithiasis in Adults.

INTRODUCTION: Ceftriaxone (CTRX) is known to occasionally cause pseudolithiasis. This condition is often observed in children; however, few studies have reported the incidence and risk factors for CTRX-associated pseudolithiasis. METHODS: In this single-center retrospective study, we investigated the incidence of and risk factors for CTRX-associated pseudolithiasis in adults. All patients underwent computed tomography to confirm pseudolithiasis before and after CTRX administration. RESULTS: The study included 523 patients. Pseudolithiasis was detected in 89 patients (17%). Data analysis showed that abdominal area-related biliary diseases at the site of infection (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.064-0.53, p = 0.0017), CTRX administration for >3 days (OR 5.0, 95% CI: 2.5-9.9, p < 0.0001), CTRX dose of 2 mg (OR 5.2, 95% CI: 2.8-9.6, p < 0.0001), fasting period >2 days (OR 3.2, 95% CI: 1.6-6.4, p = 0.0010), and estimated glomerular filtration rate <30 mL/min/1.73 m2 (OR 3.4, 95% CI: 1.6-7.5, p = 0.0022) were independent factors for pseudolithiasis. CONCLUSIONS: CTRX-associated pseudolithiasis may occur in adults and should be considered in the differential diagnosis in patients who develop abdominal pain or liver enzyme elevation after CTRX administration, particularly in patients with chronic kidney disease, in those who are fasting, in and those who receive high-dose CTRX therapy.

Gonococcal Infection of the Glans Skin, a Rare Local Complication of Gonorrhea: A Clinical Study of 13 Cases.

The study aimed to understand the incidence, site, skin lesion manifestations, and treatment of gonococcal infection of the glans skin. We enrolled men with gonococcal infection of the glans skin and men with gonococcal urethritis from January 2014 to February 2020. Demographic data, site of onset, and skin lesion manifestations were recorded for all patients. Ceftriaxone (1 g) was injected intramuscularly once daily for 5 days in patients with lesions comprising abscesses or nodules. A single dose of ceftriaxone (1 g) was injected intramuscularly in patients with pustules. Incision and drainage were performed in patients with nonruptured abscesses. Thirteen patients had gonococcal infection of the glans skin (0.65%; 95% confidence interval = [0.30, 1.01]) among 1,989 patients with gonococcal urethritis. Mean age was 35.48 ± 2.37 (range = 26-45) years. Nonmarital sexual behavior patterns were genital-genital in eight patients (61.54%) and genital-oral in five patients (38.46%). All skin lesions occurred on the ventral side of the glans. Eleven patients (84.62%) had a single lesion and two (15.38%) had multiple lesions. The lesions manifested as abscesses in five patients (38.46%), nodules in five patients (38.46%), and pustules in three patients (23.08%). All lesions exhibited tenderness. All 13 patients were cured after treatment. The study shows that gonococcal infection of the glans skin is a rare local complication of gonorrhea. Lesions often occur on the ventral side of the glans, presenting as abscesses, nodules, and pustules. Ceftriaxone treatment was effective for gonococcal infection of the glans skin.

[Drug interaction between ceftriaxone and theodrenaline/cafedrine : A case example]. / Medikamenteninteraktion zwischen Ceftriaxon und Theodrenalin/Cafedrin : Ein Fallbeispiel.

Adverse interactions between intravenous medications which are given simultaneously are a common problem in intensive care medicine. They are usually caused by administering a high number of medications over a limited number of intravenous lines or central venous catheters; however, this issue also arises in routine anesthetic procedures during surgery. The following case report highlights a so far undocumented interaction between the combination of theodrenaline/cafedrine and various antibiotics.Laparoscopic cholecystectomy was performed in a female patient, classified as ASA 1. After induction of general anesthesia 2 g ceftriaxone were administered as a perioperative antibiotic prophylaxis. Simultaneously, i.e. prior to the beginning of surgery, a mild decrease in blood pressure was observed and 2 ml diluted Akrinor® (2 ml theodrenaline/cafedrine + 8 ml NaCl 0.9%) was administered. Directly following this administration a chemical precipitation reaction occurred, and large white pasty flakes were noticed in the intravenous line. The infusion was stopped immediately and all lines were replaced.In order to confirm a causal relationship between the observed precipitation and the simultaneous administration of the two drugs, an in vitro test was performed by mixing Akrinor® with other preparations of cephalosporin antibiotics. The effect observed with ceftriaxone was reproducible and cefazoline also caused a precipitation reaction.

Hepatobiliary calculi associated with ceftriaxone treatment: An analysis of FAERS data from 2004 to 2021.

INTRODUCTION: The role of gender, age, dose and other factors in the adverse reaction process of pseudocholelithiasis caused by ceftriaxone is controversial. In this study, we further explored potential risk factors using the FAERS database. METHODS: The reported odds ratio (ROR) and the information component (IC) of specific candidate factors were calculated by using the ROR method and the Bayesian confidence promotion neural network (BCPNN) method respectively to detect potential risk factors in adverse events(AEs) of ceftriaxone and hepatobiliary calculi(HBC). One candidate factor will be considered as a suspicious signal, or potential risk factors if its lower limit of 95% confidence interval of ROR (ROR025) is greater than 1 and its lower limit of 95% confidence interval of IC (IC025) is greater than 0. RESULTS: A total of 764 AEs of HBC were used to this analysis to evaluate candidate risk factors: Age group, Gender, Dose. Child (1-12 years): male ROR025 = 6.64, IC025 = 2.42, female ROR025 = 6.66, IC025 = 2.40. Adolescent group (12-18 years): male ROR025 = 5.47, IC025 = 2.08; elderly (≥65 years): female ROR025 = 1.25, IC025 = 0.22. CONCLUSIONS: Gender was not detected as a risk factor for HBC caused by ceftriaxone. However, Male infants, male children, female children, adolescent male, and elderly female were potential risk factors for HBC caused by ceftriaxone based on criteria ROR025 > 1 and IC025 > 0.

Safety and Efficacy of Ceftriaxone in the Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections: A Noninferiority Retrospective Cohort Study.

BACKGROUND: Antistaphylococcal penicillins and cefazolin are the treatments of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections, requiring multiple doses daily. At Parkland, eligible uninsured patients with MSSA bloodstream infections (BSI) receive self-administered outpatient parenteral antimicrobial therapy (S-OPAT). Ceftriaxone was used in a cohort of S-OPAT patients for ease of once-daily dosing. OBJECTIVE: A retrospective study was conducted to evaluate clinical outcomes for patients discharged with ceftriaxone versus cefazolin to treat MSSA BSI. METHODS: A retrospective cohort noninferiority study design was used to assess treatment efficacy of ceftriaxone versus cefazolin among Parkland S-OPAT patients treated from April 2012 to March 2020. Demographic, clinical, and treatment-related adverse events data were collected. Clinical outcomes included treatment failure as defined by repeat positive blood culture or retreatment within 6 months, all-cause 30-day readmission rates, and central line-associated bloodstream infection (CLABSI) rates. RESULTS: Of 368 S-OPAT patients with MSSA BSI, 286 (77.7%) received cefazolin, and 82 (22.3%) received ceftriaxone. Demographics and comorbidities were similar for both groups. There were no treatment failures in the ceftriaxone group compared with 4 (1%) in the cefazolin group (P = 0.58). No difference in 30-day readmission rate between groups was found. The CLABSI rates were lower in ceftriaxone group (2%) compared with cefazolin (11%; P = 0.02). Limitations include retrospective cohort design. CONCLUSIONS: Ceftriaxone was found to be noninferior to cefazolin in this study. Our findings suggest that ceftriaxone is a safe and effective treatment of MSSA BSI secondary to osteoarticular or skin and soft tissue infections when used in the S-OPAT setting. POSTER ABSTRACT: OFID on 2018 Nov; 5(Suppl 1): S316: doi: 10.1093/ofid/ofy210.894.

Efficacy and Safety of Treatments for Different Stages of Syphilis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials and Observational Studies.

Parenteral penicillin is the first-line regimen for treating syphilis. However, allergic reactions and poor drug tolerance still present challenging problems with respect to use of this antibiotic. This study aimed to evaluate the efficacy and safety of ceftriaxone, erythromycin, minocycline, tetracycline, and doxycycline for syphilis treatment, compared with penicillin, to determine which antibiotic could be a better substitute for penicillin. This study included 17 articles, comprising 3 randomized controlled trials (RCTs) and 14 observational studies and involving 4,485 syphilis patients. Estimated risk ratios (RRs) and 95% confidence interval (CIs) were used to compare the serological response rates. At the 6- and 12-month follow-ups, the serological response rates were compared by direct meta-analysis and network meta-analysis (NMA). Based on direct meta-analysis, the serological response rates at the 3- and 24-month follow-ups were compared. Our NMA showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up (RR of 1.12, 95% CI of 1.02 to 1.23). Ceftriaxone was equally effective as penicillin for syphilis in terms of serological response rates, and it was a better substitute for penicillin than ceftriaxone, erythromycin, minocycline, tetracycline, or doxycycline. However, more large-scale, high-quality, double-blind trials are still needed to determine whether ceftriaxone can safely replace penicillin for the treatment of syphilis when necessary. IMPORTANCE Parenteral penicillin is the first-line regimen for syphilis treatment. However, allergic reactions and poor drug tolerance still present emerging threatening problems with respect to use of this antibiotic. Our results showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up. Sufficient data are not available for demonstrating significant differences in the efficacy of the other four antibiotics (erythromycin, minocycline, tetracycline, and doxycycline) for treating syphilis. In the clinical treatment of syphilis in patients who are allergic to penicillin or for whom penicillin is not available, ceftriaxone appears to be a better alternative treatment. This meta-analysis provides a reference for clinical treatment of syphilis. Currently, a lack of sufficient evidence to guide antibiotic treatment of syphilis exists, and a need for more high-quality RCTs is still present. This network meta-analysis can lay a foundation for further research.

Ceftriaxone compared with penicillin G for the treatment of neurosyphilis: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Neurosyphilis may cause irreversible neurological sequelae. First-line treatment consists of penicillin G, with ceftriaxone being an alternative treatment in patients allergic to penicillin. The lack of clinical data comparing the efficacy of these two drugs indicated the need for comparative clinical trials to improve national treatment guidelines in China. METHODS/DESIGN: In this multicenter randomized controlled clinical trial, 290 patients newly diagnosed with neurosyphilis will be randomized 1:1 to treatment with aqueous crystalline penicillin G (ACPG) or ceftriaxone. Patients will be treated with standard regimens of ACPG or ceftriaxone according to Chinese National Guidelines and will be followed up for 12 months. All clinical parameters will be assessed at baseline and at follow-up 3, 6, 9, and 12 months later. The primary outcomes will include cerebrospinal fluid (CSF) white blood cell (WBC) count, serological efficacy, and clinical efficacy. The secondary outcomes will include CSF protein concentrations, Mini-Mental State Examination (MMSE) scores, imaging results, recurrence, and time to recovery from neurosyphilis. Adverse events will be monitored and recorded during the trial. DISCUSSION: This trial will provide clinical data to determine whether ceftriaxone is non inferior to ACPG in treating neurosyphilis and will provide evidence for the improvement of treatment guidelines. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047164. Registered on 9 June 2021 and updated on 23 November 2021.