ro13-9904 and Cholelithiasis

Ceftriaxone is an antibiotic agent frequently used in paediatric hospital practice for the treatment of severe bacterial infections. The use of this agent can result in cholelithiasis and/or biliary sludge, more commonly in children than in adults. This systematic review was aimed at analysing available literature concerning ceftriaxone-associated biliary pseudolithiasis in paediatric patients, with a special emphasis on the clinical aspects. A literature analysis was performed using Medline and Embase electronic databases (articles published in English up to December 2019), with the search terms and combinations as follows:'ceftriaxone', 'cholelithiasis', 'biliary sludge' 'gallstones' 'neonates' 'children' 'clinical aspects' 'management'. Several case reports, case series and prospective/retrospective studies have documented a relationship between ceftriaxone treatment and biliary pseudolithiasis in the paediatric population, even though literature data regarding neonates and infants are scarce. Ceftriaxone-associated biliary pseudolithiasis is dose-dependent and usually asymptomatic but, sometimes, it may present with abdominal pain, nausea and emesis. Abdominal ultrasonography should be performed when this complication is suspected. Generally, ceftriaxone-associated cholelithiasis resolves over a variable period of time (days to months) after cessation of therapy. Therefore, a conservative approach to this condition is advocated, but a prolonged follow-up may be necessary. A personalized assessment of factors predisposing to ceftriaxone-associated biliary pseudolithiasis before prescribing the drug can allow to minimize the risk of developing it, with significant advantages in terms of human and economic costs.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child; Cholelithiasis; Humans

Bile supersaturation is necessary for cholesterol gallstones to form. Not all people with supersaturated bile form gallstones, however, and additional factors must be present. The role of pronucleating substances has been extensively studied. Of these, proteins, especially mucin, are best understood. Mucin is secreted by the gallbladder epithelium and may act as a nidus for crystal nucleation. Other proteins that may act as pronucleators include alpha 1-acid glycoprotein, alpha 1-antichymotrypsin, phospholipase C, and a small calcium binding protein. The role of antinucleating factors is less well understood. Certain drugs, including octreotide and ceftriaxone, may also predispose to stone formation. Another local factor is gallbladder stasis, a well-known risk factor for pigment stone formation. More recent research has focused on the role of bacterial infection, which has long been believed to be a factor in pigment gallstone formation. Newer data also support a role for infection in cholesterol gallstone pathogenesis. Additionally, genetic factors that may predispose a patient to cholesterol gallstones have been identified in mice and in humans.

Topics: Animals; Apolipoproteins E; Ceftriaxone; Cephalosporins; Cholelithiasis; Gastrointestinal Agents; Humans; Infections; Mice; Octreotide; Risk Factors

A multicenter, open labelled, randomized study was carried out to compare the prophylactic efficacy of Cefepime and Ceftriaxone in patients undergoing biliary tract surgery. Two hundred and nine patients were included in the study and randomized to receive preoperative infusion of 2 g Cefepime (n=107) or 2 g Ceftriaxone (n=102) both in a single i.v. administration. Antimicrobial prophylaxis was successful in preventing infections in 98.9% of patients in the Cefepime group and 97.7% in the Ceftriaxone group (p=0.3871). Both regimens were well tolerated without any adverse drug-related reactions. A single dose of Cefepime seems to be a very useful alternative to other regimens for antibiotic prophylaxis of postoperative infectious complications in the elective surgical treatment of cholelithiasis.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Cefepime; Ceftriaxone; Cephalosporins; Cholelithiasis; Female; Humans; Injections, Intravenous; Male; Middle Aged; Postoperative Complications

Ceftriaxone is a widely used third-generation cephalosporin. In this prospective study, we used sonography to investigate the incidence and outcome of biliary complications in children receiving ceftriaxone therapy.. Ceftriaxone was administered intravenously at a dosage of 100 mg/kg/day for 1-3 weeks to 118 children hospitalized for severe infection. Serial gallbladder sonograms were obtained on days 1, 5-7, and 10-14 of therapy and the day after therapy ended if it had lasted more than 2 weeks. When sonographic abnormalities were found, additional sonograms were obtained every 3 days until the abnormalities had completely resolved.. Twenty patients (17%), all asymptomatic, demonstrated sonographic abnormalities: 8 had gallbladder sludge, defined as echogenic material without associated acoustic shadowing, and 12 had pseudolithiasis, defined as echogenic material with acoustic shadowing. These abnormalities spontaneously resolved within 2 weeks of stopping the ceftriaxone (mean time to disappearance, 8.2 +/- 3.4 days). No significant differences were found between patients with normal versus abnormal sonographic findings in sex, age, duration of treatment, or other risk factors for drug precipitation.. Ceftriaxone-associated biliary pseudolithiasis is usually asymptomatic and was rapidly reversible after cessation of therapy in this group of Turkish children.

Topics: Adolescent; Ceftriaxone; Chemical Precipitation; Child; Child, Preschool; Cholelithiasis; Female; Gallbladder; Humans; Incidence; Infant; Male; Prospective Studies; Remission, Spontaneous; Ultrasonography

Ceftriaxone has potent activity against a broad range of Gram-positive and Gram-negative bacteria. While it is eliminated mainly by the kidney, 10-20% of the drug is eliminated in the bile and ceftriaxone salt precipitates have been described in the gallbladder of animals dosed with ceftriaxone. The purpose of the present study was to investigate the incidence of biliary lithiasis 6 and 12 months after treatment with ceftriaxone and to compare it with that in patients treated with amoxycillin/clavulanate. Biliary ultrasonography was performed at the start of treatment, at 6 months and at 12 months after the beginning of the study. One hundred patients were randomized and 74 were evaluable: 34 were given amoxycillin/clavulanate, 40 ceftriaxone. Gallbladder lithiasis developed in one patient 12 months after the amoxycillin/clavulanate treatment and in none in the ceftriaxone treatment arm. Biliary precipitate during ceftriaxone treatment was not looked for because this phenomenon was not known at the beginning of the study, but gallbladder precipitation that was seen in two patients given ceftriaxone during and at the end of treatment, respectively, resolved spontaneously. In conclusion, ceftriaxone treatment does not appear to lead to gallstone formation more often than an antibiotic that is not eliminated through the bile.

Topics: Adolescent; Adult; Aged; Amoxicillin; Bacterial Infections; Ceftriaxone; Cholelithiasis; Clavulanic Acid; Clavulanic Acids; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic

Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy. To examine this phenomenon further, serial gallbladder sonograms were evaluated in 44 adult patients who received intravenous ceftriaxone at 2 g or a placebo daily for 14 days in a double-blind controlled study. Ultrasound examinations of gallbladders were performed on days 1 and 14 of therapy and 2 weeks posttherapy if abnormalities were observed on day 14. Eight patients were unevaluable because of abnormal base-line gallbladder sonograms. Thirty-six patients (ceftriaxone, n = 28; placebo, n = 8) demonstrated normal baseline gallbladder sonograms and were evaluated for the development of change. A total of 6 of 28 (21.4%) ceftriaxone-treated patients and 1 of 8 (12.5%) patients who received the placebo demonstrated abnormal gallbladder sonograms on day 14 (P = 0.491). Four of the six ceftriaxone-treated patients demonstrating abnormal sonograms were clinically asymptomatic, while two patients reported vomiting. The abnormal sonograms of gallbladders of patients treated with ceftriaxone returned to normal between 9 and 26 days posttherapy. These data suggest an association between ceftriaxone treatment and the development of gallbladder abnormalities on ultrasound examination which resolve spontaneously on discontinuation of ceftriaxone therapy.

Topics: Adult; Bile Duct Diseases; Ceftriaxone; Cholelithiasis; Double-Blind Method; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Ultrasonography

To compare ceftriaxone with cefuroxime for the treatment of meningitis, we conducted a study in which 106 children with acute bacterial meningitis were randomly assigned to receive either ceftriaxone (100 mg per kilogram of body weight per day, administered intravenously once daily; n = 53) or cefuroxime (240 mg per kilogram per day, administered intravenously in four equal doses; n = 53). The mean age of the children was 3 years (range, 42 days to 16 years), and the characteristics of the two treatment groups were comparable at admission. Excluded from the study were eight other children who died within 48 hours of admission. After 18 to 36 hours of therapy, cultures of cerebrospinal fluid remained positive for 1 of the 52 children (2 percent) receiving ceftriaxone for whom cultures were available and 6 of 52 (12 percent) receiving cefuroxime (P = 0.11). In both groups the mean duration of antibiotic therapy was 10 days. The clinical responses to therapy were similar in the two treatment groups, and all 106 children were cured. Reversible biliary pseudolithiasis was detected by serial abdominal ultrasonography only in the children treated with ceftriaxone (16 of 35 vs. 0 of 35; P less than 0.001). The treatment of three children was switched from ceftriaxone to alternative antibiotics because these children had upper abdominal pain. Other side effects were infrequent in both groups. At follow-up examination two months later, moderate-to-profound hearing loss was present in two children (4 percent) treated with ceftriaxone and in nine (17 percent) treated with cefuroxime (P = 0.05); other neurologic abnormalities were similar in the two treatment groups. We conclude that ceftriaxone is superior to cefuroxime for the treatment of acute bacterial meningitis in children and that the benefits of milder hearing impairment and more rapid sterilization of the cerebrospinal fluid with ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.

Topics: Adolescent; Bacterial Infections; Ceftriaxone; Cefuroxime; Cephalosporins; Cerebrospinal Fluid; Child; Child, Preschool; Cholelithiasis; Female; Hearing Loss, Sensorineural; Humans; Infant; Injections, Intravenous; Male; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Multicenter Studies as Topic; Prospective Studies; Random Allocation

Topics: Adult; Ceftriaxone; Cholelithiasis; Clinical Trials as Topic; Female; Humans; Male; Prospective Studies; Time Factors

The success of perioperative prophylaxis in gallbladder surgery was examined in two prospective randomized studies with a total of 326 patients. Postoperative wound-healing impairments did not occur in any of the patients receiving a single preoperative application of an antibiotic with a high biliary elimination rate (ceftriaxone or apalcillin). 11% of a control group without prophylactic antibiotic application evidenced infectious wound-healing disturbances.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Bile Duct Diseases; Ceftriaxone; Cholelithiasis; Double-Blind Method; Female; Humans; Male; Middle Aged; Naphthyridines; Postoperative Complications; Premedication; Prospective Studies; Random Allocation; Wound Healing

In the course of 1 year, 180 patients undergoing elective surgery for confirmed cholelithiasis were included in a prospective randomized study in which they either received 2 g of preoperatively applied ceftriaxon intravenously at the beginning of anesthesia or, as an alternative, no antibiotic at all. Infectious wound-healing disturbances occurred postoperatively in 11% in the control group and in no case in the prophylaxis group. The difference is statistically significant.

Topics: Adolescent; Adult; Aged; Cefotaxime; Ceftriaxone; Cholecystectomy; Cholelithiasis; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Premedication; Prospective Studies; Random Allocation; Surgical Wound Infection

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.

Topics: Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Child; Cholelithiasis; Humans; Retrospective Studies; Risk Factors

The prevalence of cholelithiasis in developed countries is high and its cause is multifactorial, with a negligible proportion of drug-induced cholelithiasis.. Relevant studies were identified by PubMed, Google Scholar and Science Direct. Reference lists of retrieved articles were also reviewed. The most relevant and up-to-date information was incorporated.. There is a wide range of drugs that can induce lithiasis. While the risk of developing lithiasis is high with some drugs (ceftriaxone, atazanavir, somatostatin analogues), it is lower or even questionable with others. Some drugs precipitate in the bile and may account for up to 100% of the weight of the stone.. Cholelithiasis can be induced by a wide range of drugs with different mechanisms of action. The aim of the article is to draw attention to this lesser known fact and the need to take into account the risk of developing lithiasis prior to therapy initiation.

Topics: Bile; Ceftriaxone; Cholelithiasis; Humans; Lithiasis

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.

Topics: Aged; Ceftriaxone; Cholelithiasis; Cohort Studies; Female; Humans; Male; Renal Dialysis; Retrospective Studies; Risk Factors

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.. 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.. 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.. The high-density sludge pattern is the most common typical CT finding of CTRX-associated pseudolithiasis in adults.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftriaxone; Cholelithiasis; Female; Gallbladder; Gallbladder Diseases; Humans; Male; Middle Aged; Tomography, X-Ray Computed

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Cholangiopancreatography, Magnetic Resonance; Cholangitis; Cholelithiasis; Female; Humans; Pressure Ulcer; Tomography, X-Ray Computed

To evaluate the actual incidence of both microlithiasis and acute cholecystitis during treatment with intravenous ceftriaxone in a new rabbit model.. New Zealand rabbits were treated with intravenous ceftriaxone or saline for 21 days. Ultrasound monitoring of the gallbladder was performed every seven days until the 21st day when histopathology, immunohistochemistry for proliferating cell nuclear antigen (PCNA), pro-caspase-3 and CD68, liver enzyme biochemistry, and chromatography analysis of the bile and sediments were also performed.. All animals treated with ceftriaxone developed acute cholecystitis, confirmed by histopathology (P<0.05) and biliary microlithiasis, except one that exhibited sediment precipitation. In the group treated with ceftriaxone there was an increase in pro-caspase-3, gamma-glutamyl transpeptidase concentration, PCNA expression and in the number of cells positive for anti-CD68 (P<0.05). In the ceftriaxone group, the cholesterol and lecithin concentrations increased in the bile and a high concentration of ceftriaxone was found in the microlithiasis.. Ceftriaxone administered intravenously at therapeutic doses causes a high predisposition for lithogenic bile formation and the development of acute lithiasic cholecystitis.

Topics: Administration, Intravenous; Animals; Anti-Bacterial Agents; Ceftriaxone; Cholecystectomy; Cholecystectomy, Laparoscopic; Cholecystitis, Acute; Cholelithiasis; Disease Models, Animal; Gallbladder; Rabbits; Translational Research, Biomedical

Cholelithiasis is one of the side-effects of ceftriaxone (CTRX). Reportedly, the cholelithiasis resolves relatively soon after cessation of CTRX, hence, it is called pseudolithiasis. Previous reports have suggested that biliary pseudolithiasis can cause not only gallstone attacks, but also severe adverse events, such as cholecystitis and pancreatitis. The purpose of this study was to prospectively elucidate the risk factors and clinical features of CTRX-associated pseudolithiasis in pediatric patients.. We prospectively examined the incidence and clinical outcome of CTRX-associated biliary pseudolithiasis. Subjects included infants and children who were admitted to hospital with acute disease. Ultrasonography was used to confirm the absence of stones and sludge in the gallbladder before CTRX therapy, and in assessment of pseudolithiasis on days 3, 5, 7 and 10 after initiation of CTRX in all subjects. The pseudolithiasis group was then compared with the non-pseudolithiasis group in terms of age, sex, CTRX dose, CTRX duration, duration of fever, fasting period, period of bed rest, and blood test results.. Sixty patients were enrolled in the study. Eleven of them had biliary pseudolithiasis on ultrasonography (18.3%). Formation of biliary pseudolithiasis was prevalent in the fasting and bed rest groups, appearing relatively early in these groups.. Special attention should be paid to the degree of oral intake and patient activity when CTRX is prescribed. We recommend regular ultrasonographic follow up of patients receiving CTRX, to evaluate the formation of biliary pseudolithiasis.

Topics: Adolescent; Anti-Bacterial Agents; Bed Rest; Ceftriaxone; Child; Child, Preschool; Cholelithiasis; Dose-Response Relationship, Drug; Fasting; Female; Follow-Up Studies; Humans; Incidence; Japan; Male; Prospective Studies; Risk Assessment; Risk Factors; Time Factors

Ceftriaxone has been associated with development of pseudolithiasis. In our institution, it is used for treatment of perforated appendicitis in children. This study evaluated the occurrence of ceftriaxone-related pseudolithiasis in this population.. After obtaining IRB approval, we performed a retrospective chart review over 51 months. We included patients undergoing laparoscopic appendectomy for perforated appendicitis. All patients were treated with ceftriaxone post-operatively. Patients without initial or post-treatment gallbladder imaging available for review were excluded.. There were 71 patients who met inclusion criteria with a mean (±SD) age of 10.8 ± 3.8 years. Of these, 14 % (n = 10) developed stones or sludge in the gallbladder. The mean duration of ceftriaxone therapy was 8.7 ± 3.8 days. The average time to post-antibiotic imaging was 11.5 ± 10.3 days from initiation of antibiotics. There was no significant difference in duration of ceftriaxone therapy in the children that developed pseudolithiasis or sludge (10.0 ± 4.9 days) compared to those that did not (8.5 ± 3.6, p = 0.26). One child (10 %) with pseudolithiasis went on to become symptomatic, requiring a laparoscopic cholecystectomy.. In our experience, ceftriaxone use for perforated appendicitis is associated with a significant incidence of biliary pseudolithiasis, and is unrelated to duration of ceftriaxone therapy.

Topics: Anti-Bacterial Agents; Appendicitis; Ceftriaxone; Child; Cholelithiasis; Female; Follow-Up Studies; Humans; Male; Retrospective Studies; Time Factors

Topics: Abdominal Pain; Adolescent; Anti-Bacterial Agents; Ceftriaxone; Cholelithiasis; Emergency Service, Hospital; Gallbladder; Humans; Male; Ultrasonography

We report a case of a 47-year-old female patient with ceftriaxone (CTRX)-associated pseudolithiasis. CTRX was administered at a dosage of 2g/day for 8 days because of colonic diverticulitis. A routine abdominal computed tomography (CT) scan was performed to investigate the diverticulitis. However, the CT scan demonstrated stones and sludge in the gallbladder, which had not been present before CTRX administration. Therefore, we diagnosed the patient with pseudolithiasis caused by CTRX and stopped CTRX administration. The stones and sludge disappeared 6 days after stopping CTRX administration. This underreported adverse effect of CTRX should be considered when treating both children and adult patients.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cholelithiasis; Diagnosis, Differential; Diverticulitis, Colonic; Female; Humans; Middle Aged

Topics: Anti-Bacterial Agents; Ceftriaxone; Child, Preschool; Cholelithiasis; Humans; Male; Nephrotic Syndrome

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Cholelithiasis; Female; Humans

Biliary microlithiasis is an uncommon but recognized cause of upper abdominal pain, cholecystitis, cholangitis, and pancreatitis in adults. Gallstones smaller than 3 mm may not be seen on transabdominal ultrasound and may only be seen on endoscopic ultrasound. This condition is poorly described in children. The aim of this study is to review the results of laparoscopic cholecystectomy to treat biliary microlithiasis in a pediatric case series.. We performed a retrospective case review of children with biliary microlithiasis who were treated with laparoscopic cholecystectomy.. Three children were diagnosed with biliary microlithiasis. Two patients had recurrent right upper quadrant pain and nausea. A third patient had midepigastric pain and idiopathic pancreatitis. All 3 had a normal gallbladder on transabdominal ultrasound. Additional imaging with hepatobiliary scan, computed tomography, and magnetic resonance cholangiopancreatography revealed no biliary source for symptoms. Endoscopic ultrasound was performed on all 3 children, demonstrating microlithiasis of the gallbladder. Each child had a laparoscopic cholecystectomy with intraoperative cholangiogram. No abnormalities were seen on intraoperative cholangiogram. All 3 children had alleviation of pain and improvement of symptoms in postoperative follow-up.. Children with biliary microlithiasis and associated clinical symptoms can be successfully treated with laparoscopic cholecystectomy. Endoscopic ultrasound should be considered in the evaluation of the child with clinical biliary symptoms and a negative transabdominal ultrasound result.

Topics: Adolescent; Age of Onset; Antibiotic Prophylaxis; Ceftriaxone; Child; Cholagogues and Choleretics; Cholangiography; Cholangiopancreatography, Magnetic Resonance; Cholecystectomy, Laparoscopic; Cholelithiasis; Combined Modality Therapy; Comorbidity; Endosonography; False Negative Reactions; Female; Follow-Up Studies; Humans; Male; Neurosurgical Procedures; Pancreatitis; Postoperative Complications; Radiography, Interventional; Retrospective Studies; Technetium Tc 99m Lidofenin; Tomography, X-Ray Computed; Ursodeoxycholic Acid

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Cholelithiasis; Community-Acquired Infections; Female; Humans; Infant; Infusions, Intravenous; Injections, Intravenous; Male; Meningitis, Bacterial; Pneumonia, Bacterial; Urinary Tract Infections

Two patients, a girl and a boy, both aged 8.5 years, presented with serious side effects caused by ceftriaxone and co-trimoxazole, respectively. The first patientwas treated with ceftriaxone (100 mg/kg/day with a body weight of 35.6 kg) on suspicion of a neuroborreliosis, but developed an acute cholecystitis with cholelithiasis 3 weeks after the antibiotic had been withdrawn. He underwent a laparoscopic cholecystectomy. Ceftriaxone binds calcium in the biliary tract, forming biliary sludge or stones. The second patient developed thrombocytopenia during treatment with co-trimoxazole (58 mg/kg/day with a body weight of 25.4 kg) because of a urinary-tract infection. After discontinuation of the co-trimoxazole the thrombocytopenia resolved spontaneously. The pathophysiological mechanism involved may be either a direct toxic effect of trimethoprim or an immune-mediated reaction to sulfamethoxazole. According to current guidelines, the dosage of the drug was too high in both cases. It is important to ensure a correct dosage in children, since side effects are potentially dose-related.

Topics: Anti-Bacterial Agents; Body Weight; Ceftriaxone; Child; Cholelithiasis; Dose-Response Relationship, Drug; Female; Humans; Male; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Cholecystectomy, Laparoscopic; Cholecystitis, Acute; Cholelithiasis; Humans; Male; Necrosis

Ceftriaxone is known to induce reversible precipitations, known as pseudolithiasis, in the gallbladder and urinary tract. The aim of this study was to investigate the incidence and predisposing factors that contribute to this side effect.. A prospective study was conducted in 156 children admitted for the treatment of various infections with different daily ceftriaxone doses (50 mg/kg, 75 mg/kg, and 100 mg/kg). Sonographic examinations of the gallbladder and urinary tract were performed before treatment on the third and seventh day of therapy, and at the first and second month after the end of treatment. Patients with positive findings were followed with weekly sonographic examinations until the abnormality resolved.. Abnormal gallbladder sonograms were demonstrated in 27 children (17%); 16 of them (10%) had gallbladder lithiasis, 11 had gallbladder sludge (7%) (n = 4 on the third day, n = 23 on the seventh day), and 1 developed urolithiasis (0.6%). Five children (19%) were symptomatic. The abnormalities resolved after a mean of 16 days (range 10-30 days). Patients with pseudolithiasis were older and treated with higher drug doses than those with normal sonographic findings (P < 0.01 and P < 0.05, respectively).. Biliary pseudolithiasis (and infrequently nephrolithiasis) usually occurs in children receiving high doses of ceftriaxone. It is generally asymptomatic. When this reversible complication becomes symptomatic, unnecessary cholecystectomy should be avoided.

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Cholelithiasis; Dose-Response Relationship, Drug; Female; Gallbladder; Humans; Infant; Male; Prospective Studies; Ultrasonography; Urinary Tract; Urolithiasis

Topics: Anti-Bacterial Agents; Biliary Tract Diseases; Ceftriaxone; Child; Cholelithiasis; Colic; Female; Humans; Time Factors; Ultrasonography

It is well known that ceftriaxone leads to pseudolithiasis in some patients. Clinical and experimental studies also suggest that situations causing gallbladder dysfunction, such as fasting, may have a role for the development of pseudolithiasis. In this study, we prospectively evaluated the incidence and clinical importance of pseudolithiasis in paediatric surgical patients receiving ceftriaxone treatment, who often had to fast in the post-operative period. Fifty children who were given ceftriaxone were evaluated by serial abdominal sonograms. Of those, 13 (26%) developed biliary pathology. Comparison of the patients with or without pseudolithiasis revealed no significant difference with respect to age, sex, duration of the treatment and starvation variables. After cessation of the treatment, pseudolithiasis resolved spontaneously within a short period. The incidence of pseudolithiasis is not affected by fasting.

Topics: Adolescent; Age Factors; Ceftriaxone; Child; Child, Preschool; Cholelithiasis; Fasting; Female; Humans; Incidence; Male; Postoperative Complications; Remission, Spontaneous; Sex Factors; Time Factors; Ultrasonography

In neurosurgery, ceftriaxone is a widely used, third generation cephalosporin for the treatment of CNS infections and perioperational prophylaxis. Recent studies have demonstrated that ceftriaxone induces reversible precipitates in the gallbladder. This complication is referred to as "biliary pseudolithiasis", and it has symptoms similar to the raised intracranial pressure (ICP) symptoms of the perioperative period. Symptomatic biliary pseudolithiasis should be kept in mind in all pediatric neurosurgery cases under ceftriaxone therapy in order to prevent unnecessary postoperative investigations and surgery.

Topics: Adolescent; Ceftriaxone; Cephalosporins; Cerebral Ventricle Neoplasms; Child; Cholelithiasis; Diagnosis, Differential; Encephalocele; Humans; Intracranial Hypertension; Intracranial Pressure; Magnetic Resonance Imaging; Male; Neurosurgical Procedures; Tomography, X-Ray Computed; Ultrasonography

Topics: Anti-Bacterial Agents; Ceftriaxone; Child; Cholelithiasis; Female; Humans

Cholelithiasis is a rare condition seen during childhood. The aim of this study was to determine frequency of biliary sludge and cholelithiasis with ceftriaxone therapy.. Thirty-eight children aged between 1 month and 17 years were evaluated with ultrasonographic examination at the initiation of the ceftriaxone therapy and 10th day of therapy, consecutively. If biliary sludge or cholelithiasis were demonstrated, scans were repeated monthly until pathology disappeared.. Abnormal gallbladder sonograms were demonstrated in 36.8% (n = 14) of patients at the 10th day of therapy. Cholelithiasis was detected in 28.9% (n = 11) of patients and biliary sludge was detected in 7.9% (n = 3). Two children still had cholelithiasis at the 30th day after therapy and one had cholelithiasis after the 60th day. The 9-year-old girl who still had cholelithiasis after 60 days of therapy also had nausea, vomiting and abdominal pain at 7 days after cessation of therapy. Her 90th day sonographic examination was normal.. Reversible biliary sludge or pseudocholelithiasis due to ceftriaxone treatment is not a rare condition. Therefore it is benign, spontaneously resolved and clinical signs are usually absent.

Topics: Anti-Bacterial Agents; Bile; Ceftriaxone; Child, Preschool; Cholelithiasis; Female; Gallbladder; Humans; Male; Prospective Studies; Time Factors; Ultrasonography

Topics: Ceftriaxone; Cephalosporins; Child; Cholelithiasis; Humans; Ultrasonography

A 64 years diabetic man presented with recurrent episodes of fever and abdominal pain. Ultrasonography revealed the presence of an abscess in the right lobe of the liver and a distended gall bladder with multiple calculi. Salmonella typhi was grown from the liver aspirate. Cholelithiasis may act as a predisposing factor for hepatic abscess formation in Salmonella carriers.

Topics: Ceftriaxone; Cephalosporins; Cholelithiasis; Diabetes Complications; Follow-Up Studies; Humans; Liver Abscess; Male; Middle Aged; Salmonella typhi; Time Factors; Typhoid Fever; Ultrasonography

Treatment with ceftriaxone may be accompanied by precipitation of ceftriaxone calcium salts in the gallbladder, called pseudolithiasis. We present a case, in which a formerly healthy five year-old girl developed symptomatic pseudolithiasis during treatment with Rocephalin. The symptoms and pseudolithiasis disappeared after a few days with symptomatic treatment and change of antibiotics.

Topics: Ceftriaxone; Cephalosporins; Cholelithiasis; Female; Humans; Ultrasonography

Up to 40% of ceftriaxone is excreted unchanged into the bile and, due to its high calcium-binding affinity, it may form a salt that can provoke biliary lithiasis. Echography revealed that biliary lithiasis was present in 12-45% of patients treated with ceftriaxone as early as the second day of treatment. Lithiasis is usually asymptomatic and disappears in less than 2 months. Symptomatic cases and patients requiring cholecystectomy have been described in the literature. We present four children, evaluated in 1999, who presented asymptomatic cholelithiasis between the second and fourth day of ceftriaxone treatment. Biliary lithiasis was found after 2-4 days of treatment, with resolution of the lithiasis between 1-4 months after the end of therapy.

Topics: Ceftriaxone; Cephalosporins; Child; Child, Preschool; Cholelithiasis; Humans; Male; Ultrasonography

The prolonged biological half-life of Ceftriaxone, allowing once-daily dosing, has contributed to the large diffusion of this third-generation cephalosporin in children. Ceftriaxone is known to induce reversible precipitates in the gallbladder of adults and children. A prospective study was conducted during 1997 in 34 children admitted for the treatment of acute pyelonephritis. Ceftriaxone (intravenous daily single-dose of 50 mg/kg under 2g/day) was initially used. A first gallbladder sonogram, performed before the first or second injection, was normal in all cases. A second evaluation was performed before the fifth and last injection. On this second evaluation the presence of one (n = 3) or two gallstones was recorded in 5 children (15%) on a sonogram made after 3 (n = 4) or 5 (n = 1) injections. Their median age was 7 years (range 4 months to 11 years). All five children remained symptom-free and the normalization of the sonographic patterns was constant on the last sonogram performed 2 (n = 1), 3 (n = 2) and 5 months (n = 2) after discontinuation of Ceftriaxone. This study confirms the possibility of precocious biliary lithiasis under Ceftriaxone therapy in childhood and their spontaneous dissolution after discontinuation of the drug. They seem unpredictable and independent of the age, sex in a cohort homogeneous for the nature of the infection, modality of a short- and low-dose therapy. Clinicians and radiologists should be aware of this complication as an etiology of a so-called primary cholelithiasis and to prevent anxiety or unnecessary cholecystectomy. The antibacterial and pharmacokinetic benefits of Ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.

Topics: Acute Disease; Ceftriaxone; Child; Child, Preschool; Cholelithiasis; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infant; Infusions, Intravenous; Male; Prospective Studies; Pyelonephritis; Risk Factors; Ultrasonography

Topics: Ceftriaxone; Cephalosporins; Child; Cholelithiasis; Escherichia coli Infections; Female; Humans; Pyelonephritis; Risk Factors; Time Factors

Topics: Adult; Ceftriaxone; Cephalosporins; Cholelithiasis; Female; Humans; Kidney Failure, Chronic

Cholelithiasis is uncommon in childhood and usually associated with any predisposing factors such as congenital abnormalities of biliary tract, hemolytic diseases, TPN administration and diseases of terminal ileum. Recent studies demonstrated ceftriaxone inducing reversible precipitations in gallbladder that mimic cholelithiasis. This complication is termed "biliary pseudolithiasis" or "reversible cholelithiasis". In this paper we describe a patient who developed biliary pseudolithiasis after six days of ceftriaxone therapy which completely resolved eleven days after the end of the treatment, and discuss the indication for cholecystectomy.

Topics: Adolescent; Ceftriaxone; Cephalosporins; Cholelithiasis; Diagnosis, Differential; Gallbladder; Humans; Hypospadias; Male; Surgical Wound Infection; Ultrasonography

We prospectively evaluated the incidence of gallbladder pseudolithiasis in children treated with high doses of ceftriaxone for a variety of serious infections. We also monitored the time interval needed for this phenomenon to develop and resolve completely after initiation and cessation of treatment, respectively. Included in this study are 44 children treated with ceftriaxone 100 mg/kg/d divided into 2 equal intravenous doses and followed by serial abdominal sonography. Eleven children developed pseudolithiasis of gallbladder 2-9 d after initiation of ceftriaxone therapy. Six children (54.5%) developed this complication within the first 3 d. Lithiasis completely resolved 8-23 d after the end of treatment. In conclusion, pseudolithiasis of the gallbladder developed in 25% of sick children and completely resolved in all patients. Early development of this complication was not exceptional. It occurred in more than half of these children.

Topics: Adolescent; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Cholelithiasis; Female; Humans; Infant; Infant, Newborn; Male; Prospective Studies; Time Factors; Ultrasonography; Urinary Bladder

Topics: Adolescent; Ceftriaxone; Cephalosporins; Cholelithiasis; Empyema, Subdural; Humans; Male; Pancreatitis

The authors report a case of biliary colic secondary to gallstones formed during a course of therapy with Ceftriaxone. Three weeks after cessation of therapy the gallstones dissolved.

Topics: Adult; Ceftriaxone; Cephalosporins; Cholelithiasis; Colic; Endocarditis, Bacterial; Humans; Iatrogenic Disease; Male

Patients with chronic renal failure were admitted to the Neurological Department and symptoms of cholelithiasis were observed. Ceftriaxone therapy in one case was clinically effective.

Topics: Ceftriaxone; Cephalosporins; Cholelithiasis; Female; Humans; Kidney Failure, Chronic; Middle Aged

Drug related false-positive hepatobiliary imaging is uncommon. The authors present a case of a 54-year-old woman who was treated with intravenous ceftriaxone for bacterial meningitis. Symptoms of acute cholecystitis subsequently developed and a sonogram revealed a gallstone. A Tc-99m DISIDA hepatobiliary study was positive for cystic duct obstruction. After discontinuation of ceftriaxone, the patient's clinical condition improved and, 2 weeks later, a repeat hepatobiliary scan was normal. High doses of ceftriaxone and prolonged administration may lead to formation of pseudocholelithiasis and signs of acute cholecystitis. Although this condition is usually benign and reversible, discontinuation of the drug is warranted when symptoms of acute cholecystitis are accompanied by a positive hepatobiliary scan.

Topics: Ceftriaxone; Cephalosporins; Cholecystitis; Cholelithiasis; False Positive Reactions; Female; Gallbladder; Humans; Imino Acids; Middle Aged; Organotechnetium Compounds; Radionuclide Imaging; Technetium Tc 99m Disofenin

Between July, 1992 and June, 1994, 151 pediatric patients who had ceftriaxone therapy for probable or definite bacterial enteritis were prospectively evaluated by serial abdominal ultrasonography. All patients received a dose of > or = 50 mg/kg/day and for a duration of 3 or more days. Five patients developed gallbladder precipitates or pseudolithiasis during treatment. Fasting and patients older than 24 months were probably the significant risk factors associated with this phenomenon (p < 0.05). However, no significant differences in sex, dose (50 vs. > 50 mg/kg/day) or duration of therapy (< 5 vs. > 5 day) were observed between patients who received ceftriaxone with and without the development of this gallbladder abnormality.

Topics: Adolescent; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Cholelithiasis; Female; Humans; Infant; Male; Risk Factors

Topics: Bacterial Infections; Bronchopneumonia; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Cholelithiasis; Female; Humans; Male; Risk Factors; Urinary Tract Infections

Treatment of unsubstantiated Lyme disease has led to serious complications in some cases. Two case-control studies, based on information in clinical records of patients discharged with a diagnosis of Lyme disease during 1990-1992, were conducted at a central New Jersey hospital. Twenty-five patients with biliary disease were identified, and 52 controls were selected from 1352 patients with suspected Lyme disease. Only 3% of 71 evaluatable subjects met the study criteria for disseminated Lyme disease. Patients with biliary disease were more likely than were antibiotic controls to have received ceftriaxone and more likely than ceftriaxone controls to have received a daily ceftriaxone dose > or = 40 mg/kg and to be < or = 18 years old. Fourteen of 25 biliary case-patients underwent cholecystectomy; all had histopathologic evidence of cholecystitis and 12 had gallstones. Thus, treatment of unsubstantiated diagnoses of Lyme disease is associated with biliary complications.

Topics: Adolescent; Adult; Age Factors; Case-Control Studies; Ceftriaxone; Child; Child, Preschool; Cholecystitis; Cholelithiasis; Female; Humans; Lyme Disease; Male; Middle Aged; New Jersey; Retrospective Studies; Risk Factors; Sex Factors

Ceftriaxone, a third-generation cephalosporin, is known to induce reversible precipitations in the gallbladder of children. In general, radiologic signs and symptoms will develop after 9-11 days of treatment. The authors report a case where 48 h of therapy were sufficient to develop a biliary pseudolithiasis. Clinicians and radiologists should be aware of this complication which mimics true cholelithiasis.

Topics: Ceftriaxone; Cholelithiasis; Diagnosis, Differential; Humans; Infant; Male; Streptococcal Infections

Topics: Ceftriaxone; Child; Cholelithiasis; Fever; Hiccup; Humans; Male

The term biliary pseudolithiasis was coined by Schaad (1988) to describe the appearance of gallbladder sludge following treatment with ceftriaxone. After cessation of the drug the condition resolves, hence the term "pseudolithiasis." The third generation cephalosporin, cefatriaxone, is a very potent, broad spectrum antibiotic indicated in meningitis, osteomyelitis, pyelonephritis, Lyme disease and many other severe infectious diseases. Up to 46% of those receiving this antibiotic develop gallbladder sludge. Most are asymptomatic, but a small proportion may develop right upper quadrant pain, nausea, vomiting and even cholecystitis. Ultrasonography may demonstrate many, small, echogenic particles within the gallbladder, as well as larger echogenic foci casting acoustic shadows. However, it can not differentiate these pseudostones from real stones. There are reports of surgical intervention in such cases. 2 boys, aged 5 and 10 years, respectively, treated with ceftriaxone for meningitis are presented. Both developed symptoms during treatment and in both gallbladder sludge was identified by ultrasonography. In 1 intraluminal gallbladder findings were identical with the appearance of surgical stones. Follow-up ultrasonography after the drug was stopped showed no evidence of pseudostones in either case. Awareness of this phenomena might save many unnecessary operations.

Topics: Ceftriaxone; Child; Child, Preschool; Cholelithiasis; Diagnosis, Differential; Follow-Up Studies; Gallbladder; Humans; Male; Meningitis; Ultrasonography

Topics: Ceftriaxone; Child; Cholelithiasis; Enteritis; Female; Humans; Infant; Male; Ultrasonography

Topics: Ceftriaxone; Child, Preschool; Cholelithiasis; Female; Humans

Topics: Actinobacillus Infections; Adult; Aggregatibacter actinomycetemcomitans; Ceftriaxone; Cholelithiasis; Endocarditis, Bacterial; Female; Humans

The following article describes a girl with right upper quadrant abdominal colic following Ceftriaxon therapy for purulent meningitis. Ultrasound made it possible to demonstrate sludge-balls, floating in the gallbladder, a follow up examination was normal. Moreover the features of gallbladder precipitations following Ceftriaxon therapy will be described, and the clinical consequences will be discussed.

Topics: Ceftriaxone; Child; Cholelithiasis; Colic; Female; Gallbladder Diseases; Humans; Infusions, Intravenous; Meningitis, Pneumococcal; Ultrasonography

A nine year old boy who had received Ceftriaxone for one week because of suspected bacterial meningoencephalitis developed colicky abdominal pain in the right upper quadrant two days after termination of Ceftriaxone treatment. Stones in the gallbladder were identified as cause of the abdominal symptoms. Ceftriaxone has been reported to result in so-called pseudo-lithiasis of the gallbladder in approximatively 45% of treated patients, 19% of which developed clinical symptoms. Generally, the gallstones dissolve spontaneously when Ceftriaxone treatment was of short duration.

Topics: Ceftriaxone; Child; Cholelithiasis; Colic; Fever; Headache; Humans; Male; Meningoencephalitis; Ultrasonography

Topics: Adult; Ceftriaxone; Cholelithiasis; Female; Follow-Up Studies; Humans; Lyme Disease; Remission, Spontaneous; Ultrasonography

A short-term prophylaxis based on a one-shot injection 30 min before operation of 2 g ceftriaxone has been used in 20 cases, in patients undergoing elective cholecystectomy or biliary tract surgery for gall-stones. The prophylaxis with ceftriaxone proved to be successful in all patients.

Topics: Adult; Aged; Aged, 80 and over; Antibiotic Prophylaxis; Biliary Tract Surgical Procedures; Ceftriaxone; Cephalosporins; Cholecystectomy; Cholelithiasis; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Postoperative Complications; Treatment Outcome

Ceftriaxone, a third-generation cephalosporin, has been associated with the development of sludge or stones in the gallbladders of some patients treated with this medication. Such precipitates, which are usually reversible upon discontinuation of the drug, sometimes cause symptoms, have simulated acute cholecystitis, and have even led to cholecystectomy in some cases. We report the first known instance of biliary obstruction and secondary pancreatitis in association with reversible ceftriaxone-induced pseudolithiasis.

Topics: Aged; Ceftriaxone; Cholelithiasis; Cholestasis; Female; Humans

Topics: Adult; Bilirubin; Ceftriaxone; Cholelithiasis; Humans; Male; Spectrophotometry, Infrared

Ceftriaxone, a third-generation cephalosporin, is partially excreted into bile. With its clinical use, the formation of gallbladder sludge detected by ultrasonography has been reported. Four surgical specimens were examined and no gallstones were found. Instead, fine precipitates of 20-250 microns were present. Microscopically, there was a small number of cholesterol monohydrate crystals and bilirubin granules among an abundant amount of granular-crystalline material that was not morphologically cholesterol monohydrate crystals. The chemical composition of the precipitates (n = 4) was determined. There was a small amount of cholesterol (1.7% +/- 0.8%) and bilirubin (13.9% +/- 0.74%). The major component of the precipitate was a residue. On further analysis using thin-layer chromatography, high-performance liquid chromatography, and electron microprobe analysis, the residue was identified as a calcium salt of ceftriaxone. The residue also had identical crystal morphology and chromatographic elution profile as authentic calcium-ceftriaxone standards. It is concluded that ceftriaxone, after excretion and being concentrated in the gallbladder bile, can form a precipitate. The major constituent has been identified as a ceftriaxone-calcium salt.

Topics: Bile; Calcium; Ceftriaxone; Chemical Precipitation; Cholelithiasis; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Diagnosis, Differential; Electron Probe Microanalysis; Gallbladder; Humans; Male; Microscopy, Electron, Scanning; Middle Aged; Spectrophotometry, Infrared; Ultrasonography

Serial abdominal ultrasonography was performed in 37 children being treated with ceftriaxone for serious infections. Biliary concrements developed in 16 patients, causing symptoms in 3, one of whom also had urolithiasis with renal colic and obstructive ureteropyelectasia. After cessation of ceftriaxone treatment, ultrasound abnormalities and symptoms gradually disappeared, with complete sonographic resolution after 2 to 63 days.

Topics: Adolescent; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Cholelithiasis; Diagnosis, Differential; Female; Humans; Infant; Male; Prospective Studies; Ultrasonography; Urinary Calculi

Topics: Adult; Ceftriaxone; Cholelithiasis; Female; Humans

Topics: Adult; Ceftriaxone; Cholelithiasis; Female; Humans; Lyme Disease; Male; Remission, Spontaneous

Topics: Ceftriaxone; Cholelithiasis; Diagnosis, Differential; Humans

Topics: Bile; Ceftriaxone; Cholecystectomy; Cholelithiasis; Gallbladder; Humans