Reacciones cutáneas adversas a antimicrobianos sistémicos en pacientes hospitalizados: estudio transversal analítico retrospectivo / Inpatient cutaneous adverse reactions to systemic antibiotics: an analytical cross-sectional retrospective study

Introduction: The reported literature about the types of cutaneous adverse antibiotic reactions (ATB-CAR) and the responsible antimicrobial class is scarce. Aim: to describe the clinical and histopathological profile of these reactions, and potential associations between different types of ATB-CAR and causal antibiotic class in a tertiary hospital in Chile. Material and Methods: Cross-sectional retrospective study performed at the Hospital of the Pontificia Universidad Católica de Chile. Results: A total of 58 patients were included. The most common type of ATB-CAR was morbilliform (n: 37, 63.8%). The antibiotics most frequently involved were the penicillins and cephalosporins (n: 34, 69.3%). The most common histological pattern in all types of ATB-CAR was superficial perivascular dermatitis with or without spongiosis. There was significant association between urticarial, morbilliform, DRESS and PEGA types, with the use of penicillins, cephalosporins, cotrimoxazole, and lincomycin, respectively (n: 4,100%, n: 15, 40.5%, n: 2; 50%, n: 1, 50%, p < 0.05, respectively). Discussion: This is the first description of the ATB-CAR patterns in South American hospitalized patients. Both clinical and histopathological patterns of ATB-CAR are similar to other published series, however the types of causal antibiotics are different.

Introducción: La literatura médica reportada acerca de los tipos de reacciones cutáneas adversas a antimicrobianos (ATM-cRAM) y la clase de antimicrobiano responsable es escasa. Objetivo: Describir el perfil clínico e histopatológico de estas reacciones, y establecer posibles asociaciones entre los distintos tipos de ATM-cRAM y la clase de antimicrobiano causal, en un hospital terciario en Chile. Material y Método: Estudio transversal analítico retrospectivo realizado en el Hospital de la Pontificia Universidad Católica de Chile. Resultados: Fue incluido un total de 58 pacientes. El tipo más frecuente de ATM-cRAM fue el morbiliforme (n: 37; 63,8%). Los antimicrobianos más frecuentemente implicados fueron penicilinas y cefalosporinas (n: 34; 69,3%). El patrón histopatológico más frecuente en todos los tipos de ATM-cRAM fue el de dermatitis perivascular superficial, con o sin espongiosis. Hubo asociación significativa entre las ATM-cRAM tipo urticaria, morbiliforme, DRESS y PEGA, con el uso de penicilinas, cefalosporinas, cotrimoxazol y lincomicina, respectivamente (n: 4,100%; n: 15, 40,5%; n: 2; 50%; n: 1; 50%, p < 0,05, respectivamente). Discusión: Este estudio corresponde a la primera descripción de los patrones de ATM-cRAM en pacientes hospitalizados sudamericanos. Tanto los patrones clínicos como histopatológicos de ATM-cRAM son similares a otras series publicadas; sin embargo, los tipos de antimicrobianos causales no coinciden con lo previamente descrito.

Neurotoxicidad grave por cefepime en una paciente trasplantada renal: informe de caso / Severe neurotoxicity due to cefepime in a kidney transplanted patient: case report / Neurotoxicidade grave por cefepime numa paciente transplantada renal: relatório de caso

El cefepime es un antibiótico betalactámico utilizado para tratar pacientes con infecciones complicadas. Debido a que su excreción es predominantemente renal y a que su vida media se incrementa significativamente en pacientes con deterioro de la función renal, los efectos adversos pueden ser de mayor gravedad incluyendo los de índole neurotóxica. Se informa el caso de una paciente trasplantada renal que presentó neurotoxicidad secundaria al uso de cefepime.

Cefepime is a betalactamic antibiotic used for the treatment of patients with severe infections. It is mainly excreted by the kidney, so that its half-life is significantly increased in patients with kidney failure, and in this population adverse effects may be more severe including neurotoxicity. We report the case of a kidney-transplanted patient who presented neurotoxicity associated with the use of cefepime.

O cefepime é um antibiótico betalactámico utilizado para tratar pacientes com infecções complicadas. Devido a que sua excreção é predominantemente pelo rim, sua vida média se incrementa significativamente em pacientes com deterioração da função renal em quem os efeitos adversos podem ser de maior gravidade incluindo os de índole neurotóxica. Informa-se o caso de uma paciente transplantada renal que apresentou neurotoxicidade secundária ao uso de cefepime.

Factors associated with Clostridium difficile diarrhea in a hospital in Beijing, China

Clostridium difficile is the most common cause of hospital-acquired diarrhea in patients treated with antibiotics, chemotherapeutic agents, and other drugs that alter the normal equilibrium of the intestinal flora. A better understanding of the risk factors for C. difficile-associated disease (CDAD) could be used to reduce the incidence of CDAD and the costs associated with its treatment. The aim of this study was to identify the risk factors for CDAD in a cohort of Chinese patients in a Beijing hospital. Medical charts of a total of 130 inpatients (62 males and 68 females) with hospital-acquired diarrhea (45 with CDAD; 85 without CDAD) were retrospectively reviewed. C. difficile toxins A and B were detected in fecal samples using enzyme-linked fluorescence assays. The drugs used by patients with and without CDAD before the onset of diarrhea were compared. Factors that differed significantly between the two groups by univariate analysis were analyzed by multivariate analysis using a logistic regression model. Multivariate analysis showed that cephalosporin treatment was associated with a significantly higher risk of CDAD in hospitalized patients, while treatment with glycopeptides was significantly associated with a reduction in CDAD (P<0.001 for cephalosporin; P=0.013 for glycopeptides). Our data confirmed previous findings that empirical treatment with cephalosporins is positively associated with CDAD compared to individuals using other CDAD-related drugs. Additionally, we showed that treatment with glycopeptides was negatively associated with CDAD, compared to individuals using other CDAD-related drugs.

Cefepime encephalopathy and normal renal function / Encefalopatia induzida por cefepime em um paciente com função renal normal

BACKGROUND: Several cases of cefepime neurotoxicity have been reported. Herein reported is a case of cephalosporin-associated neurotoxicity in apatient with normal renal function. CASE REPORT: A 64-year-old woman with a history of post-transplantation chronic myeloid leukemia was admittedto hospital due to hyporexia, fever, productive cough and mild dyspnea. Initial blood screen revealed pancytopenia and a normal renal function.Intravenous cefepime was empirically started and after 40 hours the patient developed sudden mental confusion. Neurological examination was normal. Cranial computed tomography and brain magnetic resonance scans were normal. Electroencephalography showed triphasic waves of diffuse slowness without ongoing epileptic activity. Lumbar puncture was normal. Cefepime neurotoxicity was promptly considered and antibiotics were switched to piperacillin and tazobactam. After five days, the patient recovered completely with remission of myoclonus. CONCLUSIONS: Awareness should be given to possible central nervous system complications induced by cefepime, especially in the elderly, even without renal failure

INTRODUÇÃO: Existem vários relatos de casos de toxicidade do sistema nervoso central induzida pelo cefepime. Relata-se um caso de toxicidade do sistema nervoso central associada ao uso de uma cefalosporina em um paciente com função renal normal. RELATO DE CASO: Uma mulher de 64 anos com história de transplante de medula óssea devido a leucemia mielóide crônica foi admitida ao hospital devido a hiporexia, febre, tosse produtiva e dispnéia leve. Os exames laboratoriais de rotina demonstraram pancitopenia e função renal normal. O cefepime intravenoso foi empiricamente iniciado e, após 40 horas da administração, o paciente apresentou quadro súbito de confusão mental. Exame neurológico foi normal, assim como a tomografia computadorizada craniana e a ressonância magnética encefálica. O eletroencefalograma demonstrou ondas trifásicas de lentificação difusa sem evidência de atividade epileptiforme. O líquor estava normal. A toxicidade do sistema nervoso central pelo cefepime foi rapidamente considerada e o antibiótico foi trocado para piperacilina e tazobactan. Após cinco dias, o paciente apresentou recuperação completa com remissão da mioclonia. CONCLUSÃO: Deve-se dar atenção às possíveis complicações do sistema nervoso central induzidas pelo cefepime, especialmente em idosos, mesmo sem insuficiência renal.

An Overlooked Cause of Impaired Consciousness in a Hemodialysis Patient

No abstract available.

Antibióticos y expresión de betalactamasas de espectro extendido (BLEE) en agentes bacterémicos / Use of antibiotics and expression of extended spectrum betalactamases (ESBL) in bacteremic agents

Objective: To evaluate the association between Escherischia Coli (E. Coli) and Klebsiella spp bacteremia, both of which produce Extended Spectrum beta-lactamases (ESBL), and the use of third generation cephalos-porines (TGC) during 30 days prior to the development of the infection. Patients and Methods: Case study of all patients hospitalized between 2004 and 2007 at Hospital de Niños Roberto del Río, who presented E. coli y Klebsiella spp bacteremia. Results: 212 episodes of E. coli o Klebsiella spp bacteremias were found; 205 contained all necessary data, 47 of which were cases and 158 were controls. The use of TGC showed a statistically significant correlation with the finding of ESBL in those patients' bacteremias (OR 2,5; IC95 percent 1,26-5). In addition, an independent statistically significant association was found with hospital acquired infections (OR 8,2; IC95 percent 2,7-27,1), and the use of Central Venous Catheter (OR 38,9; IC95 percent 14,3-106,0) became close to statistical significance. Conclusions: This study shows a statistically significant association between ESBL bacteremias and use of TGC within 30 days prior to the infection, confirming other literature reports.

Objetivo: Estudiar la asociación entre bacteriemia por E. coli y Klebsiella spp productoras de beta-lactamasas de espectro extendido (BLEE) y el uso de cefalosporinas de tercera generación (CTG) durante los 30 días previos al desarrollo de la infección. Método: Estudio caso control encestado desarrollado entre los años 2004 y 2007 en el Hospital de Niños Roberto del Río, con análisis retrospectivo de los pacientes con bacteriemias por E. coli y Klebsiella spp. Resultados: Se registraron 212 episodios de bacteriemias por E. coli o Klebsiella spp, en 205 de ellos se contó con los registros necesarios, 47 fueron casos y 158 controles. El uso de CTG se asoció de modo estadísticamente significativo con la probabilidad de aislar cepas BLEE de bacteriemias en estos pacientes (OR 2,5; IC95 por ciento 1,26-5). Además, se observó asociación independiente y estadísticamente significativa con Infección Intrahospitalaria (OR 8,2; IC95 por ciento 2,7-27,1), y el uso de Catéter Venoso Central (OR 38,9; IC95 por ciento 14,3-106,0) se acercó a la significancia estadística. Conclusiones: Nuestro trabajo establece la asociación estadística entre bacteriemia por cepas BLEE y el uso de CTG dentro de los 30 días previos al desarrollo de la infección, confirmando lo sugerido por la literatura.

Twenty autopsy cases of anaphylactic shock induced by cephalosporins / 法医学杂志

OBJECTIVE@#To explore the characteristics of autopsy cases of anaphylactic shock induced by cephalosporins and provide the evidences in forensic medicine.@*METHODS@#Twenty cases of anaphylactic shock induced by cephalosporins were collected from April 2005 to August 2009 in judicial expertise center of China Medical University, and the characteristics of the cases were analyzed retrospectively.@*RESULTS@#The age of decedents ranged from 40 to 60 years. Ninety percent of cases were from local medical centers and private clinics. The symptoms of the shock appeared 30 s-150 min after the administration of the drug, and death occurred 10 min-210 min after the appearance of the shock symptoms. In all cases, various degrees of eosinophil infiltration were observed in trachea and the lungs. Serum IgE detected by ELISA method was normal value in 14 cases.@*CONCLUSION@#In fatal anaphylactic cases, little specific findings are detected during postmortem and microscope examination. For this reason, the determination of cause of death in these cases requires comprehensive analysis combined with clinic information and excludes other diseases leading to the sudden death.

Monitoramento de eventos adversos em ambiente hospitalar: relato de farmacovigilância, São Paulo / Monitoring of adverse events in hospitals: report of pharmacovigilance, São Paulo

Introdução: O percentual de internações hospitalares devido às reações adversas (RA) a medicamentos em alguns países é cerca de 10% (OPAS/OMS) e acarreta gastos adicionais para o sistema de saúde. Objetivo: Determinar medicamentos mais envolvidos em RA e as RA mais comuns. Métodos: Realizou-se um monitoramento descritivo de RA em hospital privado de São Paulo, de 2004 a 2008, em 197 leitos, totalizando 100 notificações. Dados descritos em frequência (n de RA relatadas). Resultados: Os medicamentos mais envolvidos em RA foram:cefalosporinas (13%) e quinolonas (12%). As RAs foram: rash cutâneo (20%), prurido (13%), hiperemia (12%), náusea (10%), tremores (9%), placas eritematosas (6%), etc. Observou-se que 61% dos indivíduos com RA são do sexo feminino. Conclusão: Sugere-se uma atitude positiva em farmacovigilância, para que a notificação se torne rotina. Verificou-se que houve crescimento das notificações. Pacientes do sexo feminino apresentaram mais RA e os antibióticos foram os medicamentos com maior RA.

Introduction: According to PAHO/WHO, the hospital admissions? due to adverse drug reactions (ADR) in some countries is around 10%, resulting in additional costs for health system. Objective: To determine which drugs are involved in adverse drug reactions and the most common reactions. Methods: We conducted a descriptive monitoring of ADR in a private hospital in São Paulo (Brazil), from 2004 to 2008, in 197 beds, totaling 100 notifications. Data described in frequency (n ADR reported). Results: The drugs most commonly involved in ADR were cephalosporins (13%) and quinolones (12%). The adverse reactions were rash (20%), pruritus (13%), redness (12%), nausea (10%), tremors (9%), erythematous plaques (6%), etc. We observed that 61% of individuals with ADR are female. Conclusion: Achieve the development of positive attitude towards pharmacovigilance among healthcare professionals to ADR becomes accepted and understood. There was an increase in notifications, antibiotics are involved in ADR and female have more ADR.

Alta correlación entre el consumo de ciprofloxacina y la prevalencia de Klebsiella pneumoniae productora de ß-lactamasas de espectro extendido / High relationship between ciprofloxacin use and prevalence of ESBL Klebsiella pneumoniae

Background: To assess the relationship between ciprofloxacin use and the prevalence of extended spectrum betalactamases (ESBL) Klebsiella pneumoniae. Patients and Methods: Semestral mean values regarding use of antibiotic and prevalence of ESBL Kp were compared during 9 semesters using linear regression and coefficient of correlation. Results: The only statistically significant correlation was ciprofloxacin use and ESBL(+) K. pneumoniae prevalence, with a coefficient of correlation of 0.86 and p = 0.0027 using linear regression. Conclusions: Ciprofloxacin use must be taking into account when considering infection control programs due to high prevalence rates of ESBL(+) K. pneumoniae in the hospital setting.

Fundamento: Evaluar la correlación entre el consumo de cefalosporinas de tercera generación y ciprofloxacina con la prevalencia de cepas de Klebsiella pneumoniae productoras de ß-lactamasas de espectro extendido (BLEE). Pacientes y Métodos: Los valores promedios semestrales, correspondientes a consumo y prevalencia se compararon durante 9 semestres, usando coeficiente de correlación y regresión lineal. Resultados: La única asociación que resultó estadísticamente significativa, fue la correspondiente al consumo de ciprofloxacina y K. pneumoniae BLEE (+), con un coeficiente de correlación de 0,86 y una p de 0,0027, en el análisis de regresión lineal. Conclusiones: El consumo de ciprofloxacina debe ser tenido en cuenta al momento de establecer programas de control de infecciones frente a elevadas tasas de prevalencia de K. pneumoniae productoras de BLEE en un hospital.

Allergy to beta-lactams in pediatrics: a practical approach

OBJETIVO: Apresentar uma abordagem prática ao diagnóstico e conduta na alergia a antibióticos beta-lactâmicos. FONTES DOS DADOS: Periódicos da área de alergia indexados nas bases MEDLINE e LILACS, além de estudos e textos clássicos que tratam do tema. SíNTESE DOS DADOS: A alergia à penicilina é relatada com freqüência, em muitos casos resultando na exclusão desse medicamento do arsenal terapêutico. Cerca de 10 por cento dos relatos de alergia a drogas são confirmados. As manifestações clínicas decorrentes da reação alérgica à penicilina são bastante amplas, destacando-se os quadros cutâneos. Os quatro mecanismos de hipersensibilidade de Gell & Coombs estão envolvidos nas reações alérgicas. A penicilina é degradada em determinante maior (95 por cento dos produtos) e em determinantes menores (5 por cento dos produtos). As reações imediatas, mediadas por IgE, e que determinam quadros de anafilaxia, estão relacionadas aos determinantes menores em 95 por cento dos casos. A hipersensibilidade a esses produtos pode ser avaliada através de testes cutâneos realizados com os determinantes maior e menores, permitindo, assim, evitar o choque anafilático em indivíduos alérgicos. O texto ressalta conhecimentos básicos sobre a alergia à penicilina, propiciando um diagnóstico mais adequado desse evento e a conduta em casos de suspeita de alergia a beta-lactâmicos. CONCLUSÃO: O diagnóstico de alergia à penicilina tem sido feito de forma inadequada, resultando em sua exclusão do arsenal terapêutico. O melhor reconhecimento dessas condições permitirá o uso da penicilina com diminuição dos riscos decorrentes da hipersensibilidade.

OBJECTIVE: To present a practical approach to the diagnosis and management of allergy to beta-lactam antibiotics. SOURCES: Allergy journals indexed in MEDLINE and LILACS, as well as seminal studies and texts. SUMMARY OF THE FINDINGS: Allergy to penicillin is commonly reported. In many cases, this results in the decision not to use this drug. About 10 percent of drug allergy reports are confirmed. The clinical manifestations due to allergic reaction to penicillin vary widely, with emphasis on skin disorders. Gell & Coombs' four hypersensitivity mechanisms are involved in allergic reactions. Penicillin is degraded to a major (95 percent) and minor determinants (5 percent). Immediate IgE-mediated reactions causing anaphylaxis are associated with minor determinants in 95 percent of the cases. Hypersensitivity to these products can be assessed using cutaneous tests performed with major and minor determinants, thus avoiding anaphylactic shock in allergic individuals. The present article underscores the basic body of knowledge on allergy to penicillin, providing support for a more accurate diagnosis of this event and for the choice of management in cases of suspected beta-lactam allergy. CONCLUSIONS: The incorrect diagnosis of penicillin allergy frequently leads to the exclusion of this drug as a therapeutic option. A better recognition of these situations will enable the use of penicillin and reduce the risks associated with hypersensitivity.

Drug fever - A Hospital based study

To study the frequency, causative agents, symptomatology of drug fever in children. A hospital based descriptive study. The study was carried out from Jan 01,2005 to Dec 31,2005. All children examined by author were included, both in private and public sector hospitals at Hyderabad. Children 1 to 12 years of age with febrile illness of more than 10 days duration and prior use of drugs for at least 5-7 days were included in this study and were evaluated for having drug fever. 62 [0.72% of total 8560] febrile children, 32 of them males and 30 females, were diagnosed as having drug fever, with Cephalosporins being the common group responsible for causing fever in 33 [53.22%] followed by penicillins in 14 [22.60%], antituberculous in 12 [19.35%],Phenytoin in 2 [3.2%] and carbamezapine in 1 [1.61%].1] Drugs should be considered as a cause of fever of obscure origin. 2] Judicious use of drugs especially antibiotics can not be over emphasized

Encefalopatia induzida por cefepime: achados clínicos e eletroencefalográficos em sete pacientes / Cefepime-induced encephalopathy: clinical and electroencephalographic features in seven patients

Cefepime, uma cefalosporina de quarta geração, com amplo espectro de ação, é um antibiótico largamente utilizado no tratamento de infecções graves em ambientes hospitalares. O registro de segurança deste fármaco é considerado favorável. Vários casos de encefalopatia grave, associada ao uso de cefepime, reversível, foram descritos recentemente. No presente artigo, descrevemos sete casos de encefalopatia induzida por cefepime, com achados eletroencefalográficos (EEG) característicos, que apresentaram reversão do quadro com a suspensão da droga. As relações do padrão EEG encontrado nestes pacientes com estado epiléptico não-convulsivo são consideradas, bem como a possibilidade de enquadrar os pacientes estudados na entidade "encefalopatia epileptiforme".

Pediatric tonsillopharyngitis--an evaluation of cefprozil in Indian patients.

OBJECTIVE: The emergence of penicillin resistant strains and the presence of co-pathogens have made the treatment of bacterial infections in children a challenge. Streptococcal tonsillopharyngitis, which is a common infection has been well treated with cefprozil, a novel third generation cephalosporin. The aim of the present study was to evaluate cefprozil in pediatric tonsillopharyngitis. An assessment of the clinical cure and bacteriological eradication rates and an overall tolerability was made. METHODS: It was a prospective, open, non-comparative multicentric study. 316 children (mean age 6.61 years) with tonsillopharyngitis were included. Patients were given cefprozil susp 15 mg/kg/day in two divided doses a day for 10 days. RESULTS: A clinical cure of 96.6% and bacteriological eradication of 94.29% was achieved with cefprozil. Overall tolerability of cefprozil was assessed by physicians and 46% rated tolerability of cefprozil as excellent, 38% as very good, 10% as good, 6% as fair and none as poor. CONCLUSION: Cefprozil has been found to be an excellent drug of superior microbiological and clinical activity in the treatment of pediatric patients with tonsillopharyngitis. The drug also has an expanded spectrum.

A multicenter comparative study of cefepime versus broad-spectrum antibacterial therapy in moderate and severe bacterial infections

The safety and efficacy of cefepime empiric monotherapy compared with standard broad-spectrum combination therapy for hospitalized adult patients with moderate to severe community-acquired bacterial infections were evaluated. In an open-label, multicenter study, 317 patients with an Acute Physiology and Chronic Health Evaluation (APACHE II) score ranging from >5 to =19 were enrolled with documented pneumonia (n=196), urinary tract infection (n=65), intra-abdominal infection (n=38), or sepsis (n=18). Patients were randomly assigned 1:1 to receive cefepime 1 to 2 g IV twice daily or three times a day or IV ampicillin, cephalothin, or ceftriaxone ± aminoglycoside therapy for 3 to 21 days. For both treatment groups, metronidazole, vancomycin, or macrolide therapy was added as deemed necessary. The primary efficacy variable was clinical response at the end of therapy. Two hundred ninety-six (93 percent) patients met evaluation criteria and were included in the efficacy analysis. Diagnoses included the following: 180 pneumonias (90 cefepime, 90 comparator), 62 urinary tract infections (29 cefepime, 33 comparator), 37 intra-abdominal infections (19 cefepime, 18 comparator), and 17 sepses (8 cefepime, 9 comparator). At the end of therapy, overall clinical success rates were 131/146 (90 percent) for patients treated with cefepime vs 125/150 (83 percent) for those treated with comparator (95 percent confidence interval [CI]: - 2.6 percent to 16.3 percent). The clinical success rate for patients with community-acquired pneumonia, the most frequent infection, was 86 percent for both treatment groups. Among the patients clinically evaluated, 162 pathogens were isolated and identified before therapy. The most commonly isolated pathogens were Escherichia coli (n=49), Streptococcus pneumoniae (n=29), Haemophilus influenzae (n=14), and Staphylococcus aureus (n=11). Bacteriologic eradication/presumed eradication was 97 percent for cefepime vs 94 percent for comparator-treated patients. Drug-related adverse events were reported in 16 percent of cefepime patients and 19 percent of comparator patients. In conclusion, cefepime had higher cure rates compared with broad-spectrum combination therapy as an initial empiric treatment for hospitalized patients with moderate to severe community-acquired infections, including urinary tract infections, intra-abdominal infections, and sepsis

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.