Cholecystectomy during ceftriaxone therapy. A translational study with a new rabbit model

Abstract Purpose: To evaluate the actual incidence of both microlithiasis and acute cholecystitis during treatment with intravenous ceftriaxone in a new rabbit model. Methods: 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. Results: 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. Conclusion: Ceftriaxone administered intravenously at therapeutic doses causes a high predisposition for lithogenic bile formation and the development of acute lithiasic cholecystitis.

Safety and efficacy of a novel drug elores (ceftriaxone + sulbactam + disodium edetate) in the management of multi-drug resistant bacterial infections in tertiary care centers: a post-marketing surveillance study

Abstract Objective: In India, Elores (CSE-1034: ceftriaxone + sulbactam + disodium edetate) was approved as a broad spectrum antibiotic in year 2011 and is used for management of Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections in tertiary care centers. The objective of this study was to investigate the efficacy of this drug in patients with Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections and identify the incidence of adverse events in real clinical settings. Methods: This Post Marketing Surveillance study was conducted at 17 centers across India and included 2500 patients of all age groups suffering from various bacterial infections and treated with Elores (CSE1034). Information regarding demographic, clinical and microbiological parameters, dosage and treatment duration, efficacy and adverse events (AEs) associated with the treatment were recorded. Results: A total of 2500 patients were included in the study and efficacy was evaluated in 2487 patients. In total, 409 AEs were reported in 211 (8.4%) patients. The major AEs reported were vomiting (3.0%), pain at injection site (2.5%), nausea (2.3%), redness at site (1.96%), thrombophlebitis (1.4%). Of total reported AEs, 40 (5.3%) AEs were reported in pediatric, 310 (20.6%) in adult, and 59 (23.6%) in geriatric group. No AE belonging to grade IV or V was reported in any patient. In terms of efficacy, 1977 (79.4%) patients were cured, 501 (20.1%) patients showed clinical improvement and 5 (0.2%) patients were complete failure. The treatment duration varied from 5 to 7 days in different patients depending on the infection type. Conclusion: In this post-marketing surveillance study, CSE-1034 was found to be an effective and safe option against Pip tazo and meropenem in management of patients with multi-drug resistant (MDR) bacterial infections under routine ward settings.

Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos en pediatría: Caso clínico / DRESS syndrome in paediatrics: Clinical case

El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos es una enfermedad potencialmente mortal, caracterizada por exantema, fiebre, adenopatías, alteraciones hematológicas y compromiso de órganos internos. Objetivo: Presentar una afección poco frecuente en pediatría para facilitar la sospecha diagnóstica y el rápido reconocimiento por parte de los médicos. Caso clínico: Lactante de 9 meses hospitalizada por un cuadro de neumonía viral grave con ventilación mecánica no invasiva, tratada con ceftriaxona entre otros medicamentos. Al quinto día de suspendido el antibiótico presentó un exantema maculopapular violáceo, confluente de predominio en el tronco, la cara y las extremidades superiores, asociado a fiebre, eosinofilia y elevación de transaminasas. Se manejó con prednisona oral más corticoides tópicos por 6 semanas, con buena evolución a los 3 meses de seguimiento. Conclusiones: El diagnóstico de síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos se realiza por clínica y exámenes de laboratorio, además de biopsia cutánea en caso de duda diagnóstica. Si bien su causa más frecuente son los anticonvulsivantes se han descrito casos con un sinnúmero de fármacos. El manejo consiste en la suspensión del fármaco sospechoso asociado a medidas de soporte y tratamiento corticosteroide por tiempos prolongados.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially life-threatening, drug-induced hypersensitivity reaction that includes skin eruption, haematological abnormalities, lymphadenopathy, and internal organ involvement. Objective: Presenting a rare condition in children, to facilitate a rapid diagnostic suspicion and recognition by doctors. Case report: An 9 months old infant admitted due to a severe viral pneumonia, managed with non-invasive ventilation and ceftriaxone. Five days after stopping antibiotics, a confluent maculopapular rash appeared, which was predominantly in the trunk, face and upper extremities, combined with a fever, eosinophilia, and elevated serum levels of transaminase. She received treatment with oral prednisone and topical corticosteroids for 6 weeks, with a good outcome after 3 months. Conclusions: The diagnosis of DRESS syndrome is made using clinical criteria, laboratory values, and histopathology, if there is any query. Although it is classically caused by anticonvulsants and sulphonamides, many other drugs have been implicated. The offending drug should be immediately discontinued and the patient given supportive treatment, and systemic corticosteroids for long periods of treatment.

Acute generalized exanthematous pustulosis x Von Zumbusch’s pustular psoriasis: A diagnostic challenge in a psoriatic patient

AbstractSevere cutaneous drug reactions include a wide spectrum of clinical manifestations ranging from mild morbilliform cutaneous rash, to severe forms of hypersensitivity. Special attention is given in this report to the acute generalized exanthematous pustulosis (AGEP), induced in 90% of cases by the use of systemic drugs, especially aminopenicillins and macrolides. The incidence of the disease is low, 1-5 cases per million patients / year. The main differential diagnosis is Von Zumbusch's Pustular Psoriasis. The prognosis is generally good and the disease self limited, after withdrawal of the triggering drug. In this report the authors describe a case of AGEP, triggered by ceftriaxone in a patient with psoriasis vulgaris.

Clinical Review and Case Report of Ceftriaxone-associated Gallbladder Pseudolithiasis in Adult / 대한소화기학회지

Although ceftriaxone can be used safely in most instances, it can sometimes induce biliary sludge or stone formation. Most of the patients remain asymptomatic and children are more susceptible to develop this condition, but adults can be affected as well. Because sludge or stones disappear after discontinuing ceftriaxone, this condition is referred to as ceftriaxone-associated pseudolithiasis. A 54-year-old woman was admitted to a local clinic for management of ileus. During admission, she had received ceftriaxone and metronidazole, and had been on nil per os for the past 6 days. She was then referred to our hospital for cholecystectomy due to persistent right upper quadrant pain. Although imaging studies showed gallbladder sludge, pseudolithiasis was suspected because of ceftriaxone administration history and prolonged fasting. After careful watch-and-wait, the condition resolved spontaneously after ceftriaxone discontinuation. Our clear understanding on ceftriaxone-associated gallbladder pseudolithiasis allowed us to avoid an unnecessary cholecystectomy. Herein, we report the case of a 54-year-old woman with ceftriaxone-associated gallbladder pseudolithiasis that was successfully managed by ceftriaxone discontinuation alone.

Ceftiaxone-Induced Neurotoxicity: Case Report, Pharmacokinetic Considerations, and Literature Review

Ceftriaxone is widely used in patients for the treatment of serious gram-negative infections. Ceftriaxone can induce some potential side effects, including neurotoxicity, however, nonconvulsive status epilepticus has rarely been reported. We report a case of acute reversible neurotoxicity associated with ceftriaxone. A 65-yr-old woman with chronic kidney disease developed altered consciousness during ceftriaxone treatment for urinary tract infection. The electroencephalogram demonstrated continuous bursts of generalized, high-voltage, 1 to 2 Hz sharp wave activity. Neurologic symptoms disappeared following withdrawal of ceftriaxone. The possibility of ceftriaxone-induced neurotoxicity should be considered in patients developing neurological impairment during ceftriaxone use, and the discontinuation of the drug could lead to complete neurological improvement.

Anemia hemolítica autoimune induzida por ceftriaxona: relato de caso e breve revisão da literatura / Ceftriaxone-induced immune hemolysis: case report and a concise review of the literature

JUSTIFICATIVA E OBJETIVOS: As cefalosporinas de segunda e terceira geração têm sido descritas como a causa mais comum de anemia hemolítica (HA) induzida por fármacos. A AH causada por ceftriaxona apesar de ser um evento raro, vem sendo descrita tanto em crianças quanto em adultos sendo estes a maioria idosa, acima de 60 anos. A apresentação clínica da AH induzida pelo ceftriaxona é usualmente abrupta com palidez, taquipneia,parada cardiorrespiratória e choque. O objetivo deste estudo foi relatar um caso de AH autoimune associada ao ceftriaxona com evolução fatal e breve revisão da literatura. RELATO DO CASO: Paciente do sexo feminino, 55 anos, com diagnóstico de infecção urinária apresentou AH autoimune intravascular com hemoglobina de 4,5 g/dL, após infusão de ceftriaxona não sobrevivendo ao evento apesar de todo o suporte intensivo. CONCLUSÃO: O ceftriaxona é um fármaco comumente usado e pode causar AH fatal; o reconhecimento precoce da AH e a instituição de suporte intensivo são fundamentais para a tentativa de um prognóstico mais favorável.

BACKGROUND AND OBJECTIVES: The second and third generation cephalosporins have been reported as the most common cause of drug-induced hemolytic anemia (HA). The ceftriaxone-induced HA despite being a rare event, has been described both in children and adults and these mostly elderly above 60 years. The clinical presentation of ceftriaxone-induced HA isusually abrupt with pallor, tachypnea, cardio-respiratory arrestand shock. We report here a ceftriaxone-induced HA case withfatal outcome and a concise review of the literature. CASE REPORT: Female patient, 55 years, with urinary infection had HA autoimmune intravascular resulting in hemoglobinof 4.5 g/dL, after ceftriaxone infusion, not surviving the event despite all the intensive care. CONCLUSION: Ceftriaxone is a drug commonly used and can cause fatal HA; early recognition of HA and the institution of intensive support are essential for attempting a more favorable prognosis.

Litiasis biliar asociada a ceftriaxona en pediatría: reporte de dos casos y revisión de la literatura / Biliary lithiasis due to ceftriaxone treatment in pediatric: report of two cases and literature review

Introducción: La ceftriaxona es una cefalosporina de tercera generación, bactericida, de amplio espectro de acción y de una vida media larga, por lo que es utilizada ampliamente en pediatría. Un efecto colateral poco conocido de este fármaco es la formación de precipitaciones biliares. Objetivo: Presentar 2 casos clínicos de pacientes de 9 y 14 años que cursaron con litiasis vesicular asintomática durante el tratamiento con ceftriaxona, y que tuvieron una resolución espontánea antes de 30 días. La revisión de la literatura muestra que la detección de precipitaciones biliares ocurre en un 14-47 por ciento de los pacientes tratados con ceftriaxona, los factores de riesgo de desarrollarlas es una mayor edad, tratamiento prolongado y dosis alta. Su resolución es espontánea y precoz. Conclusión: La formación de precipitaciones biliares si bien es frecuente, la mayoría de las veces es asintomática y de resolución espontánea, por lo que ceftriaxona sigue siendo un antibiótico seguro.

Introduction: Ceftriaxone is a third-generation cephalosporin, with a wide spectrum of action and a prolonged half-life time. These properties have contributed to its widespread use in pediatric patients.An infrequent collateral effect is the development of biliary pseudolithiasis. The aim is to present two cases of 9 and 14 years old, with asymptomatic gallstones during treatment with ceftriaxone, andresolved spontaneously before 30 days. Material and methods: Literature review shows that biliary pseudolithiasis occurs between 14 percent to 47 percent of patients treated with ceftriaxone. Risk factors are older age, long treatment, and high doses. Its resolution is early and spontaneous. Conclusion: Formation of biliary pseudolithiasis although frequent, most of the times is asymptomatic and resolves spontaneously, therefore ceftriaxone remains as safe antibiotic.

Evaluation of Ceftriaxone Utilization at Multicenter Study

BACKGROUND/AIMS: As bacterial resistance to antimicrobial agents has grown due to the increasing use of antimicrobial agents, we sought to evaluate the suitability of ceftriaxone usage (representative of third generation cephalosporins) at 10 university hospitals in Korea. METHODS: We prospectively evaluated the appropriateness of antibiotic usage in 400 adult patients who received ceftriaxone between February 1, 2006 and June 30, 2006. Drug utilization evaluation (DUE) methods were based on standards set forth by the American Society of Hospital Pharmacists. The DUE criteria used in this study were modified to be more suitable in our hospital setting: justification of drug use, critical and process indications, complications, and outcome measures. RESULTS: The average patient age was 64.4 years. The utilization of ceftriaxone was appropriate in 262 cases (65.5%) for the justification of use, while inappropriate use was observed in 138 cases (34.5%). Common reasons for inappropriate use of ceftriaxone included continued empiric use for presumed infections, prophylactic perioperative injection, and empiric therapy for fever. Most of the critical indications showed a high rate of suitability (66.5-98.5%). Complications occurred in 37 cases (9.3%). With respect to outcome measures, clinical responses were observed in 60.7% of cases, while only 15.7% of cases showed evidence of infection eradication via negative cultures. CONCLUSIONS: Appropriate use (65.5%) of ceftriaxone was higher than inappropriate use (34.5%) at university hospitals in Korea. Inappropriate utilization, however, including continued empiric use for presumed infections and prophylactic perioperative injection remained high. Intensification of educational programs and antibiotic control systems for ceftriaxone is needed to improve the suitability of antimicrobial use.

Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 ± 19.8) were administered IVA (500mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study - EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1 percent) completed the study. At the end of treatment, 95.2 percent (CI95: 88.9 percent - 100 percent) reported cure or clinical improvement; at the end of the study, that figure was 88.9 percent (CI95: 74.1 percent - 91.7 percent). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40 percent), and 8 reported presumed eradication (53.3 percent). At end of study evaluation, 9 patients showed pathogen eradication (50 percent), and 7 showed presumed eradication (38.89 percent). Therefore, negative cultures were obtained from 93.3 percent of the patients at EOT, and from 88.9 percent at the end of the study. One patient (6.67 percent of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11 percent) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3 percent of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin...

Colelitíase associada ao uso de ceftriaxona / Cholelithiasis associated with the use of ceftriaxone

Crianca de sete anos recebeu ceftriaxona para o tratamento de meningite, evoluindo com dor em hipocôndrio direito associada a cálculo na vesícula biliar. Após três meses, a ultrassonografia abdominal foi normal. O conhecimento de que a ceftriaxona pode levar ao surgimento de colelitíase pode evitar intervencões cirúrgicas desnecessárias.

Acute generalized exanthematous pustulosis (AGEP): case report

A pustulose exantemática aguda generalizada (AGEP) é uma dermatose induzida por droga, caracterizada por episódio agudo de aparecimento de pústulas estéreis sobre base eritemato-edematosa, acompanhado de febre. Este quadro regride espontâneamente após a suspensão da droga ou em resultado do tratamento com corticóide sistêmico. As principais drogas envolvidas são agentes antifúngicos, antiinflamatórios não hormonais, analgésicos, antiarrítmicos e anticonvulsivantes. Histologicamente caracteriza-se por vasculite associada a pústulas subcórneas não foliculares. Relatamos caso de paciente branca, feminina, que se apresentou com lesões pustulosas generalizadas após o uso de cefalosporina. O diagnóstico foi confirmado pelos achados clínicos e histológicos; pela resolução do quadro após a suspensão da droga e pela introdução de corticóide sistêmico, e pela recorrência após a introdução de droga similar. A importância do reconhecimento deste tipo de dermatose induzida por droga reside na necessidade importante de seu diagnóstico diferencial, clínico e histológico, com a psoríase pustulosa generalizada e a pustulose subcórnea, particularmente no que tange às opções terapêuticas que se apresentam para o tratamento das mesmas.

Ceftriaxone Induced Immune Hemolytic Anemia: Detection of Drug-dependent Antibody by Ex-vivo Antigen in Urine

There have been a few reported cases of immune hemolytic anemia induced by ceftriaxone. We encountered a patient with immune hemolytic anemia that seemed to be stimulated by a degradation product of ceftriaxone. The patient's direct antiglobulin test was positive only for C3d, and no ceftriaxone-dependent antibodies were detectable in the patient's serum. To demonstrate the presence of the ceftriaxone-induced antibodies, an ex-vivo antigen in urine was obtained from the patient. In addition, we prepared a 1 mg/mL suspension solution of ceftriaxone, and group AB serum as a complement source. Using several combinations of the above reactants, the indirect antiglobulin test was performed. Only the indirect antiglobulin test using the patient's serum with the ex-vivo urine antigen was found to be positive. Other combinations were not reactive. To our knowledge, this is the first reported case in Korea, in which the causative antibody appeared to be stimulated solely by a degradation product of ceftriaxone.

Ceftriaxone Induced Immune Hemolytic Anemia: Detection of Drug-dependent Antibody by Ex-vivo Antigen in Urine

There have been a few reported cases of immune hemolytic anemia induced by ceftriaxone. We encountered a patient with immune hemolytic anemia that seemed to be stimulated by a degradation product of ceftriaxone. The patient's direct antiglobulin test was positive only for C3d, and no ceftriaxone-dependent antibodies were detectable in the patient's serum. To demonstrate the presence of the ceftriaxone-induced antibodies, an ex-vivo antigen in urine was obtained from the patient. In addition, we prepared a 1 mg/mL suspension solution of ceftriaxone, and group AB serum as a complement source. Using several combinations of the above reactants, the indirect antiglobulin test was performed. Only the indirect antiglobulin test using the patient's serum with the ex-vivo urine antigen was found to be positive. Other combinations were not reactive. To our knowledge, this is the first reported case in Korea, in which the causative antibody appeared to be stimulated solely by a degradation product of ceftriaxone.

Pseudolitiasis biliar inducida por ceftriaxona / Ceftriaxone induced pseudolithiasis: a case report

Se presenta el caso clínico de una escolar portadora de una pleuroneumonia derecha en tratamiento con ceftriaxona que presentó dolor en el hipocondrio derecho y vesícula palpable 60 horas después de la administración de tres dosis terapéuticas de la droga. El estudio ecográfico abdominal reveló la presencia de pseudolitiásis o barro biliar. La suspensión del medicamento permitió una remisión rápida de la sintomatología biliar y un control ecográfico alejado mostró la normalización de la vesícula biliar. Además se describen y discuten la reversibilidad de los síntomas biliares y las anomalías ecográficas de la pseudolitiasis inducida por ceftriaxona