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.

Acute localized exanthematous pustulosis caused by cefoperazone and sodium sulbactam

Abstract Acute localized exanthematous pustulosis is a localized variant of acute generalized exanthematous pustulosis, which is characterized by the eruption of multiple scattered pustules following drug administration. A 72-year-old woman presented with multiple erythematous pustules on her face, which had appeared two days after using cefoperazone and sodium sulbactam. Histopathological findings showed subcorneal pustules and mixed inflammatory cell infiltration in the dermis. The pustules resolved within about two weeks after the patient discontinued the antibiotics. This report discusses the case of a woman with a cutaneous drug reaction consistent with acute localized exanthematous pustulosis that occurred after cefoperazone and sodium sulbactam were administered.

Síndrome DRESS com manifestação renal grave: relato de caso / DRESS syndrome with several renal involvement: case report

Reação a fármacos com eosinofilia e sintomas sistêmicos, também chamada de síndrome DRESS, é uma reação adversa grave a fármacos, idiossincrática e com envolvimento de múltiplos órgãos. Os critérios diagnósticos incluem dermatose induzida por fármaco, anormalidades hematológicas e comprometimento sistêmico. A síndrome pode levar a altas taxas de mortalidades e não identificada precocemente. O objetivo deste estudo foi descrever o caso de um paciente que desenvolveu a síndrome DRESS depois do uso de antibiótico para tratamento de úlcera em membro inferior. Paciente do sexo masculino, negro, 70 anos, apresentou síndrome DRESS após o uso de ampicilina +sulbactam para quadro de úlcera venosa infectada em membro inferior direito. O caso compreendia eritrodermia com lesões erosadas e acometimento mucoso, caracterizando eritema multiforme major, eosinofilia >1.500cel./dL e lesão renal aguda. Foi tratado com prednisona oral (1mg/kg/dia), com remissão das lesões cutâneas, melhora da função renal e redução da leucocitose e eosinofilia. Relatou-se um caso clássico, cursando com síndrome DRESS e responsivo à corticoterapia oral. O tratamento com corticoide permanece controverso, devendo-se avaliar orisco-benefício em cada caso.(AU)

Drug reaction with eosinophilia and systemic symptoms, also calledDRESS syndrome is a severe adverse reaction to medication,idiosyncratic with involvement of multiple organs. Diagnosticcriteria include: drug-induced dermatosis, hematologicalabnormalities and systemic involvement. The syndrome canlead to high mortality rates if not promptly recognized. The aimof this study was to describe the case of a patient who developedDRESS syndrome after antibiotic use for lower limb ulcer. Malepatient, black, 70 years, presented DRESS syndrome after useof ampicillin + sulbactam for infected venous ulcer in the rightlower limb. The case included erythroderma with injuries anderoded mucosal involvement, featuring erythema multiformemajor, eosinophilia greater than 1,500cel/dL and acute kidneyinjury. He was treated with oral prednisone (1mg/kg/day), withremission of skin lesions, improvement in renal function andreduced leukocytosis and eosinophilia. We reported a classiccase of DRESS syndrome coursing with acute kidney injury,responsive to oral steroids. The treatment with corticosteroidsremains controversial and need to evaluate the risk-benefit ratioin each case.(AU)

Penfigoide ampollar por fármacos: entidad subdiagnosticada? / Drug-Induced Bullous Pemphigoid: an Underdiagnosaed Entity?

El penfigoide ampollar (PA) es una enfermedad infrecuente, de curso crónico y benigno, que aparece en personas de edad avanzada y se caracteriza por la presencia de ampollas subepidérmicas.En términos generales, el diagnóstico de las enfermedades ampollares se basa en las manifestaciones clínicas, los hallazgos histopatológicos y la inmunofluorescencia directa. Si bien la ausencia de alguno de estos métodos puede dificultar el mismo, una adecuada correlación clínico-patológica permite, en la mayoría de los casos, arribar al diagnóstico y realizar el tratamiento apropiado. El PA puede ser causado por fármacos y produce cuadros clínicos similares al PA idiopático. A continuación se presentan dos casos con diagnóstico de penfigoide ampollar por fármacos.

Bullous Pemphigoid is a chronic, infrequent benign disease of the elderly, characterized by the presenceof subepidermal bullae. Diagnosis is based on clinical, histopathological and direct immunofluorescencefindings. Though the absence of any of them hampers the diagnosis, a correct clinico-pathologic correlation is necessary to make the appropriate treatment. Drug induced-BullousPemphigoid presents with identical clinical features as those of the Idiopathic Bullous Pemphigoid.We present two patients with drug-induced Bullous Pemphigoid.

A Case of Immune Hemolytic Anemia Induced by Ceftizoxime and Cefobactam (Sulbactam/Cefoperazone) / 대한진단검사의학회지

Simultaneous drug-induced immune hemolytic anemia (DIIHA) caused by multiple drugs is rare. We report a case of a patient who developed DIIHA caused by 2 drugs. The patient's serum exhibited agglutination of ceftizoxime- or sulbactam-coated red blood cells (RBCs; via a drug-adsorption mechanism) and of uncoated RBCs in the presence of sulbactam (via an immune-complex mechanism). Although ceftizoxime is known to exhibit a positive reaction by an immune-complex method with or without reactivity with drug-coated RBCs, this patient's antibodies were reactive only against drug-coated RBCs. On the other hand, sulbactam, which is known to cause hemolytic anemia by nonimmunologic protein adsorption, exhibited positive reactions in tests with both drug-coated RBCs and in the presence of sulbactam. This is the first report of DIIHA due to a sulbactam-cefoperazone combination and the fourth report of DIIHA due to ceftizoxime. Owing to the patient's complicated laboratory results, DIIHA was suspected only at a late stage. We propose that for the prompt diagnosis of DIIHA, tests for all possible causative drugs should be conducted by 2 methods.

Eficácia e segurança de Sultamicilina (Ampicilina/Sulbactam) e Amoxacilina/Clavulanato no tratamento das infecções de via aéreas superiores em adultos: um estudo multicêntrico, aberto e randomizado / Efficacy and safety of Sultamicillin (Ampicillin/Sulbactan) and Amoxicillin/Clavulanic Acid in the treatment of upper respiratory tract infections in adults: an open-label, multicentric, randomized trial

As IVAS em crianças e adultos são os motivos mais freqüentes de consulta médica e os que mais demandam o uso de antibióticos. A crescente resistência bacteriana causada pela produção das beta-lactamases constitui um dos mais sérios problemas atuais. A Sultamicilina é uma pró-droga dupla da ampicilina e do sulbactam, um potente inibidor de beta-lactamases que pode fazer frente a estas dificuldades. OBJETIVO: avaliar a eficácia, segurança e tolerabilidade da Ampicilina/Sulbactan comparada à Amoxacilina/Acido Clavulânico no tratamento de IVAS, em adultos. METODOLOGIA: 102 pacientes com diagnóstico de IVAS foram randomizados em dois grupos recebendo Ampicilina/Sulbactan ou Amoxacilina/Clavulanato por 10 dias. Foram avaliados 10 e 30 dias após para análise da resposta terapêutica. RESULTADOS: Não houve diferença entre os grupos com relação à proporção de pacientes curados ao final do tratamento (visita 2) ou do estudo (visita 3). No grupo que recebeu Amoxacilina/Clavulanato, as proporções de cura foram de 61.7 por cento e 93.2 por cento nas visitas 2 e 3, comparadas a 64.4 por cento e 97.4 por cento, respectivamente, no grupo que recebeu Ampicilina/Sulbactan. A proporção de pacientes que experimentou pelo menos um evento adverso foi semelhante nos dois grupos (p = 0.940). A diarréia foi significativamente mais freqüente no grupo Amoxacilina-Clavulanato (70.6 por cento) do que no grupo Ampicilina/Sulbactan (29.4 por cento), (p=0.0164). CONCLUSÕES: A Ampicilina/Sulbactan é tão segura e eficaz quanto a Amoxacilina/Clavulanato no tratamento empírico de IVAS em adultos. A ocorrência significativamente menor de quadros de diarréia no grupo recebendo Ampicilina/Sulbactan necessita confirmação em estudos posteriores.

Upper respiratory tract infections are the most common causes of medical visits in children and adults, demanding massive use of antibiotics. Bacterial resistance caused by beta-lactamase is one of the most serious problems in this matter. Sultamicillin, a double pro-drug of Ampicillin/Sulbactan, is a potent beta-lactamase inhibitor which can face this challenge. AIM: evaluate efficacy, safety and tolerability of Ampicillin/Sulbactan compared to Amoxicillin/Clavulanate in upper respiratory tract infections in adults. METHODS: 102 patients were enrolled and randomized to receive Ampicillin/Sulbactan or Amoxicillin/Clavulanate during 10 days. They were evaluated 10 and 30 days after treatment to learn about the therapeutic response. RESULTS: There were no differences between the two groups respecting cure at the end of treatment (visit 2) or at the end of the study (visit 3). Cure ratio was 61.7 percent and 93.2 percent (visits 2 and 3) in the Amoxicillin/Clavulanate group compared to 64.4 percent and 97.4 percent, respectively, in Ampicillin/Sulbactan group. The adverse events ratio for the two groups was the same (p=0.940). The number of patients with diarrhea was greater in the group of patients receiving Amoxicillin/Clavulanate (70.6 percent) than in the group receiving Ampicillin/Sulbactan (29.4 percent) (p=0.0164). CONCLUSIONS: Ampicillin/Sulbactan is as safe and efficient as Amoxicillin/Clavulanate in the empiric treatment of upper respiratory infections in adults. The low occurrence of diarrhea in the group receiving Ampicillin/Sulbactan needs confirmation in other studies.