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.

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.

Treatment options for neonatal infections in the post-cefotaxime era.

INTRODUCTION: Cefotaxime has been used for the management of neonatal infections since the 1990s for suspected meningitis and to mitigate gentamicin-associated renal injury. Its shortage in 2015 and subsequent removal from the U.S. pharmaceutical market forced providers to consider alternatives. Ceftriaxone, a cephalosporin with an identical antibacterial spectrum of activity to cefotaxime, is contraindicated in neonates due to its risk of biliary pseudolithiasis. Ceftazidime was recommended as an alternative by the American Academy of Pediatrics but is inequivalent. AREAS COVERED: This article addresses indications for cephalosporin use and considerations when selecting an alternative to cefotaxime. Differences among cefotaxime, ceftriaxone, ceftazidime, and cefepime are discussed and compared to the standard-of-care presumptive regimen, ampicillin, and gentamicin. The authors consider the data behind the neonatal contraindication to ceftriaxone and provide recommendations for their application to practice. EXPERT OPINION: The data against ceftriaxone use in neonates remain poor, particularly in the context of the cefotaxime shortage and lack of an equivalent alternative. Ceftriaxone could be considered in low-risk neonates without hyperbilirubinemia or exposure to calcium-containing fluids on a case-by-case basis. Ceftazidime monotherapy for presumptive management of neonatal infections is inappropriate; cefepime should be more frequently utilized in neonates who are poor candidates for ceftriaxone.

Acute necrotizing calculous cholecystitis after treatment with ceftriaxone in an elderly patient: a case report.

BACKGROUND: Ceftriaxone, a third-generation cephalosporin antibiotic with a long plasma half-life, is widely used to treat various infections. The use of ceftriaxone can sometimes induce biliary sludge or stone formation. Although most cases of ceftriaxone-induced pseudolithiasis are asymptomatic or mild and resolve with discontinuation of the drug, we experienced an elderly case of severe acute necrotizing calculous cholecystitis after administration of ceftriaxone. CASE PRESENTATION: A 72-year-old male patient was admitted to our hospital because of acute diverticulitis in ascending colon. Ceftriaxone was administered at a dose of 2 g/day for 6 days. Although he recovered after therapy, he was readmitted about 2 weeks later because of severe pain with rebound tenderness in the right upper quadrant. An abdominal imaging study revealed stones and sludge in the gallbladder that were not observed before starting ceftriaxone therapy. Therefore, antibiotic treatment with flomoxef 2 g/day was indicated. However, on the fifth day of readmission, the peritoneal irritation symptoms in the right upper quadrant worsened, and elevated inflammatory response and liver dysfunction were observed. Cholecystectomy was performed based on these findings. The resected inflamed gallbladder showed acute necrotizing cholecystitis with sand granular gallstones. A comparative analysis of the infrared spectroscopic pattern of the composition of gallstones collected during surgery with that of the ceftriaxone powder revealed that both have very similar infrared spectroscopic patterns. CONCLUSIONS: Ceftriaxone-related pseudolithiasis is generally reversible and mainly observed in children. Here, we report a rare case of ceftriaxone-related acute necrotizing cholecystitis in an elderly patient. We confirmed that the stones in the gallbladder are composed of ceftriaxone. The older age, dehydration, fasting, and long-time bed rest during the administration of high-dose ceftriaxone were the potential risk factors for gallstone formation.

Pseudolithiasis of gall bladder induced by perioperative administration of ceftriaxone sodium:report of three cases / 中华全科医师杂志

Three patients received surgical treatment in Department of Hepatobiliary Surgery of Mengchao Hepatobiliary Hospital from December 2020 to February 2022. Ceftriaxone sodium was given prophylactically before and after operation,and gallbladder silt stones were found by imaging examination on the 3rd, 3rd and 2nd after surgery in 3 patients, respectively. No special treatment was given,after the withdrawal of ceftriaxone sodium for 28, 38 and 48 d,radiographic examination showed that calculi disappeared spontaneously. It is suggested that the pseudolithiasis may be related to administration of ceftriaxone sodium.

Ceftriaxone-associated Pseudolithiasis in Elderly People: Frequency and Risk Factors.

Objective Ceftriaxone (CTRX) is a widely used antibiotic because of its long plasma half-life and good tissue transmission. Many of the reported studies on CTRX-associated pseudolithiasis were performed in children. Although some studies have been published in adults, there are no studies limited to elderly people. The present study investigated CTRX-associated pseudolithiasis and explored its risk factors in the elderly. Methods We retrospectively reviewed 133 elderly patients (≥65 years old) treated with CTRX. Pseudolithiasis was defined as stones or sludge newly appearing in the gallbladder, as detected by computed tomography after the administration of CTRX. We evaluated the risk factors for pseudolithiasis using multivariate regression and inverse probability of treatment weighting analyses. Results Among the 133 patients, 24 (18%) developed CTRX-associated pseudolithiasis. In a multivariate analysis, the CTRX dose [odds ratio (OR) 4.54, 95% confidence interval (CI) 1.36-15.07, p=0.012] and CTRX treatment duration (OR 2.80, 95% CI 1.06-8.04, p=0.043) were significantly associated with pseudolithiasis formation. The cut-off value of the total CTRX dose associated with pseudolithiasis formation was 19 g. A propensity analysis determined that the frequency of pseudolithiasis was increased in patients treated with >19 g total CTRX compared with those who received ≤19 g in total (OR 4.06, 95% CI 1.45-11.32, p=0.008). Conclusion The incidence rate of CTRX-induced pseudolithiasis is high in elderly people, and the CTRX dose and CTRX treatment duration are significant risk factors for pseudolithiasis. A total dose of >19 g increases the likelihood of pseudolithiasis formation in elderly people treated with CTRX.

Ceftriaxone-associated pseudolithiasis.

Ceftriaxone-associated pseudolithiasis.

Ceftriaxone pseudolithiasis detected by computed tomography and followed up until resolution.

Introduction: Ceftriaxone is a third-generation cephalosporin antibiotic that has been widely used to treat various infectious diseases. We report a case of ceftriaxone pseudolithiasis that was detected by computed tomography (CT) and followed up until it was resolved. Case: A 76-year-old woman with diabetes mellitus and renal impairment, but no history of gallstones, was diagnosed with septic shock due to renal and lung abscesses and treated with ceftriaxone. On day 22 after admission, abdominal CT revealed a gallstone, which increased in size up to day 50. Ceftriaxone was stopped on day 50, and the gallstone resolved completely after 10 weeks. Conclusion: Ceftriaxone pseudolithiasis should be cautiously considered, specifically in a patient with renal impairment and a prolonged treatment period.

Hemodialysis as a Risk Factor for Ceftriaxone-Associated Pseudolithiasis in Adults.

Ceftriaxone-associated biliary pseudolithiasis is common among children; however, there are only a few reports of pseudolithiasis in adult patients on HD. This retrospective cohort study included 278 adult patients on ceftriaxone therapy from 1 February 2016 to 1 September 2018. Pseudolithiasis was defined as a new development of sludge or stones in the gallbladder within 60 days of ceftriaxone therapy. After excluding patients with preexisting gallstones and a history of cholecystectomy, 113 patients on maintenance HD, and another 98 patients were enrolled as the HD and control group, respectively. Thirteen patients developed pseudolithiasis. Its incidence was significantly higher in the HD group than that in the control group. Multivariate logistic regression analyses showed that development of pseudolithiasis was significantly associated with HD and ceftriaxone dose. Therefore, HD in patients receiving ceftriaxone therapy appears to be associated with a risk of pseudolithiasis. These findings highlight the need for careful follow-up.

Ceftriaxone pseudolithiasis detected by computed tomography and followed up until resolution / Journal of Rural Medicine

Introduction: Ceftriaxone is a third-generation cephalosporin antibiotic that has been widely used to treat various infectious diseases. We report a case of ceftriaxone pseudolithiasis that was detected by computed tomography (CT) and followed up until it was resolved.Case: A 76-year-old woman with diabetes mellitus and renal impairment, but no history of gallstones, was diagnosed with septic shock due to renal and lung abscesses and treated with ceftriaxone. On day 22 after admission, abdominal CT revealed a gallstone, which increased in size up to day 50. Ceftriaxone was stopped on day 50, and the gallstone resolved completely after 10 weeks.Conclusion: Ceftriaxone pseudolithiasis should be cautiously considered, specifically in a patient with renal impairment and a prolonged treatment period.

Computed tomography findings of ceftriaxone-associated biliary pseudocholelithiasis in adults.

PURPOSE: This study aimed to characterize the computed tomography (CT) findings of pseudolithiasis and investigate the outcomes and natural history in adult patients receiving CTRX therapy. METHODS: A total of 17 patients were diagnosed with CTRX-associated biliary pseudolithiasis on CT between April 2013 and March 2017. The medical records, characteristics, complications, treatment options, and outcomes of these patients were examined. Serial CT images and the form, density, and location of pseudolithiasis were reviewed by two radiologists. RESULTS: Of the 17 patients with CTRX-associated pseudolithiasis, seven were men and ten were women. The median patient age was 78 years (range 31-88 years). The median interval from CTRX administration to the diagnosis of pseudolithiasis was 10 days (range 4-32 days). The CT findings of pseudolithiasis included a sludge pattern (11 patients [64.7%]), stone pattern (two patients [11.8%]), and stone plus sludge pattern (four patients [23.5%]). Seven patients (41.2%) showed gall bladder enlargement along with a common bile duct (CBD) stone. Two patients with CBD stones underwent endoscopic CBD stone removal. The median time to pseudolithiasis resolution after CTRX cessation was 69 days. CONCLUSION: The high-density sludge pattern is the most common typical CT finding of CTRX-associated pseudolithiasis in adults.

Asymptomatic ceftriaxone-associated pseudolithiasis.

An 88-year-old woman with a history of meningioma and dementia was admitted with high fever, loss of appetite, and nausea in July. Urinary tract infection was suspected. Computed tomography (CT) showed no significant findings. Urinary findings improved with administration of ceftriaxone. However, high fever appeared on hospital day 28, and CT identified a gallbladder stone without any abdominal symptoms. We considered the possibility of ceftriaxone-associated pseudolithiasis and changed pharmacotherapy to cefmetazole. CT on day 34 showed a reduction in the size of the gallbladder stone. Ceftriaxone-associated pseudolithiasis might arise in the absence of abdominal symptoms, and clinicians should take the patient background and season into account when using this agent.

Ceftriaxone-associated pancreatitis captured on serial computed tomography scans.

A 74-year-old man was treated with ceftriaxone for 5 days and subsequently experienced epigastric pain. Computed tomography (CT) was performed 7 and 3 days before epigastralgia. Although the first CT image revealed no radiographic signs in his biliary system, the second CT image revealed dense radiopaque material in the gallbladder lumen. The third CT image, taken at symptom onset, showed high density in the common bile duct and enlargement of the pancreatic head. This is a very rare case of pseudolithiasis involving the common bile duct, as captured on a series of CT images.

Risk factors of ceftriaxone-associated biliary pseudolithiasis in adults: influence of renal dysfunction.

BACKGROUND: Ceftriaxone (CTRX) is a known cause of biliary pseudolithiasis (BPL) mainly in children. Biliary elimination of CTRX increases in patients with renal dysfunction. However, the influence of renal dysfunction on the incidence of CTRX-associated BPL has not been well investigated. The aim of this study was to investigate the cumulative incidence of CTRX-associated BPL in adults and to assess if renal dysfunction is a risk factor. METHODS: We retrospectively analyzed the medical records of 478 patients treated with CTRX to assess the incidence and risk factors of CTRX-associated BPL. We examined age, sex, body weight, dosage, and duration of CTRX therapy, and the concentrations of serum creatinine, estimated glomerular filtration rate (eGFR), albumin, and serum calcium in all the patients. The cumulative incidence of BPL was calculated using a competing risk model. The multivariate analysis of each variable for the development of BPL was assessed by a Cox proportional hazards model. RESULTS: A total of 362 patients (75.7%) had renal dysfunction (eGFR: < 60 mL/min). The cumulative incidence of BPL in patients with renal dysfunction was significantly higher than that in patients with normal kidney function (4.1 vs. 0.6%, p = 0.017). Renal dysfunction (Hazard ratio (HR) 8.14, 95% CI 1.05-63.0, p = 0.045) and female sex (HR 5.35, 95% CI 1.17-24.5, p = 0.031) were independent risk factors of CTRX-associated BPL, which was confirmed using multivariate analysis (renal dysfunction: HR 7.93, 95% CI 1.04-60.5, p = 0.046) (female sex HR 4.65, 95% CI 1.03-21.1, p = 0.046). CONCLUSIONS: Renal dysfunction is an independent risk factor of CTRX-associated BPL in adults.

Ceftriaxone-Induced Acute Pancreatitis in Patient with Liver Abscess / 대한췌담도학회지

Acute pancreatitis is a rare complication in patients treated with ceftriaxone. Precipitation of ceftriaxone in the bile causes the formation of biliary sludge leading to the development of cholangitis, cholecystitis, or pancreatitis. We treated a patient with acute pancreatitis who developed this condition after the administration of ceftriaxone. A 70-year-old man presented in a drowsy state with fever. He was diagnosed with a liver abscess and treated with intravenously administrated ceftriaxone and metronidazole. He complained of dyspepsia and epigastric pain on the 25th day of ceftriaxone administration. Laboratory examination and abdominal computed tomography revealed biliary pancreatitis. Ceftriaxone-induced acute pancreatitis was suspected, and ceftriaxone administration was immediately discontinued. Two days later, serum amylase and lipase levels recovered to within reference range, and he showed rapid resolution of symptoms. We concluded that ceftriaxone results in the formation of biliary sludge and causes serious adverse events such as cholecystitis, cholangitis and biliary pancreatitis.

Progressive Pseudolithiasis Associated with the Intravenous Administration of Ceftriaxone in Patients with Central Nervous System Infections.

We report four adult cases of ceftriaxone (CTRX)-induced pseudolithiasis and nephrolithiasis. With the exception of case 1, none of our cases showed abdominal symptoms. Our patients, who had central nervous system (CNS) infections, had been treated with CTRX (4 g/day) for 35-69 days. CTRX-induced pseudolithiasis and nephrolithiasis can appear depending on the total dose of CTRX and the duration for which it is administered. Patients with bacterial CNS infections who are treated with CTRX are typically treated with higher doses for longer periods. It should be recognized that these patients are at higher risk of developing CTRX-induced pseudolithiasis and nephrolithiasis.

A case of ceftriaxone-associated biliary pseudolithiasis in an elderly patient with renal dysfunction.

Prior literature suggests that ceftriaxone causes formation of gallbladder stones at a relatively high frequency, and when abdominal symptoms occur, prompt investigation of the gallbladder is required with institution of appropriate treatment. Aging, malnutrition, renal impairment, and sepsis are risk factors for pseudolithiasis, and prevention of these is important to suppress gallstone development.

Comparative evaluation of ceftriaxone- and cefotaxime-induced biliary pseudolithiasis or nephrolithiasis: A prospective study in 154 children.

BACKGROUND: Biliary lithiasis, or sludge, and nephrolithiasis have been reported as a possible complication of ceftriaxone therapy. However, no study related to cefotaxime-induced biliary pseudolithiasis or nephrolithiasis was observed in the literature. Therefore, we investigated the comparative formation of biliary pseudolithiasis and nephrolithiasis after cefotaxime and ceftriaxone therapies. METHODS: The patients treated with ceftriaxone or cefotaxime were enrolled during the study period. Ultrasound imaging of the biliary and urinary tract was performed in all patients before and after the treatment. The patients with a positive sonographic finding at the end of treatment were followed up with monthly ultrasonography for 3 months. RESULTS: The present study showed that abnormal biliary sonographic findings were demonstrated in 18 children (20.9%) treated with ceftriaxone, 13 (15.1%) had biliary lithiasis, 5 (5.8%) had biliary sludge and 1 (1.2%) had nephrolithiasis. Abnormal biliary sonographic findings were demonstrated in only four (5.9%) children treated with cefotaxime who had biliary sludge and only one (1.5%) had nephrolithiasis. It was observed that older age was at significantly higher risk of developing biliary sludge or stone formation. Receiver operating characteristic analysis was performed to determine the residual risk and analysis found that 4.5 years was the cut-off value for age. CONCLUSIONS: The present study is unique in the literature for reporting for the first time gall bladder sludge and nephrolithiasis associated with cefotaxime use. Therefore, patients treated with cefotaxime should be monitored for serious complications like patients treated with ceftriaxone. Nevertheless, if third-generation cephalosporin is used, cefotaxime is recommended to be used rather than ceftriaxone.

Reversible Ceftriaxone-Induced Pseudolithiasis in an Adult Patient with Maintenance Hemodialysis.

Ceftriaxone (CTRX) is a third-generation cephalosporin widely used for the treatment of bacterial infections in patients with renal disease because of its excretion by both renal and hepatic mechanisms. Biliary pseudolithiasis is a known CTRX-associated complication; however, there have been no studies of this adverse event in adult patients receiving maintenance hemodialysis. Here we report the case of a 79-year-old Japanese woman with end-stage renal disease (ESRD) receiving maintenance hemodialysis who developed CTRX-induced pseudolithiasis. The patient received CTRX for bronchial pneumonia. Fifteen days following CTRX initiation, the patient presented with stomachache. Because of the presence of one gallstone and increased gallbladder wall thickness on computed tomography scans, not detected at the onset of pneumonia, the patient was diagnosed with CTRX-induced gallbladder pseudolithiasis. CTRX was discontinued immediately. At 48 days following CTRX withdrawal, the gallstone and thickening of the gallbladder wall had completely resolved. ESRD may be a risk factor for CTRX-induced pseudolithiasis as hepatic excretion of CTRX is the predominant clearance mechanism in patients with ESRD. More attention should be paid to CTRX-induced pseudolithiasis following the use of CTRX in ESRD patients.

Adverse reaction to ceftriaxone in a 28-day-old infant undergoing urgent craniotomy due to epidural hematoma: review of neonatal biliary pseudolithiasis.

The debate as to whether to administer ceftriaxone to neonates is likely to continue. Ceftriaxone has numerous advantages for critically ill pediatric patients. However, it is also known to contribute substantially to the development of biliary pseudolithiasis. Although pediatric patients rarely develop gallbladder disorders, this complication may lead to adverse events in high-risk patients with predisposing factors, particularly in neonates and infants treated with ceftriaxone. In this paper we present an interesting case report of a 28-day-old neonate with spontaneous severe epidural hematoma who developed biliary pseudolithiasis related to the use of ceftriaxone. We also discuss the efficacy of ceftriaxone in neonates and infants. Neonatologists and pediatric intensivists should be aware of the higher risk of co-existence of hyperbilirubinemia and gallbladder disorders while using ceftriaxone in pediatric settings.