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BACKGROUND: Clostridium difficile infection (CDI) causes increased morbidity and mortality. Clinical data cannot clearly predict poor CDI outcome. Data on the value of microbiological predictors is scarce. OBJECTIVE: To identify early predictors of poor outcome of CDI. METHODS: We prospectively included patients with CDI aged >2years. Clinical, immunological (Toxin B IgG/Ig A and Toxin A IgG/Ig A), microbiological factors (bacterial load, toxin quantification, sporulation, germination, and metronidazole susceptibility) were evaluated to identify early independent predictors of poor outcome. RESULTS: We identified 204 cases of CDI; outcome was poor in 22.1%. Advanced age, presence of comorbidities, leukocytosis and high toxigenic C. difficile load were independently associated with poor outcome. We could not demonstrate this correlation for antitoxin antibodies. CONCLUSION: We identified high bacterial load as a microbiological predictor of poor outcome. We propose this factor to be included in combined clinical and microbiological prediction rules of poor outcome in CDI.

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BACKGROUND/OBJECTIVE: Standard treatment for Trichomonas vaginalis is metronidazole or tinidazole. Hypersensitivity to these drugs has been documented but is poorly understood. Desensitization is an option described in limited reports of women with hypersensitivity to nitroimidazoles. The purpose of this analysis is to improve documentation of management for trichomonas infections among women with metronidazole hypersensitivity. STUDY DESIGN: Clinicians who consulted Centers for Disease Control and Prevention concerning patients with suspected hypersensitivity to metronidazole were provided with treatment options and asked to report outcomes. RESULTS: From September 2003-September 2006, complete information was obtained for 59 women. The most common reactions were urticaria (47%) and facial edema (11%). Fifteen of these women (25.4%) were treated with metronidazole desensitization and all had eradication of their infection. Seventeen women (28.8%) were treated with alternative intravaginal drugs, which were less successful; 5 of 17 infections (29.4%) were eradicated. CONCLUSION: Metronidazole desensitization was effective in the management of women with nitroimidazole hypersensitivity.

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BACKGROUND: Hypersensitivity reactions to metronidazole are infrequently described. However, we believe that such reactions are increasing due to growing use of the drug for the treatment of amebiasis and anaerobe infections combined with other antibiotics. The present study assesses the need for oral provocation in patients with probable hypersensitivity reactions to metronidazole. METHODS: We performed cutaneous prick tests with spiramycin and metronidazole as well as epicutaneous tests with metronidazole at different concentrations in four patients with cutaneous reactions to Rhodogil (metronidazole plus spiramicyn). Controlled oral challenges were then carried out with placebo using erythromycin, spiramycin and metronidazole except in the last patient due to a positive prick test. RESULTS: Only one patient showed a positive metronidazole prick test. The epicutaneous tests were negative. All patients tolerated erythromycin and spiramycin up to therapeutic doses. Oral provocation with metronidazole proved positive, the first patient presenting a delayed exanthema and the other two early erythema and itching. CONCLUSIONS: We present four cases of cutaneous exanthemas caused by metronidazole (two early and two delayed) and probably mediated by an immune mechanism which we have only been able to demonstrate in one case. Taking into account the low sensitivity of the cutaneous tests (prick tests and epicutaneous tests), oral provocation must be considered the "gold standard" for establishing the diagnosis in many cases of hypersensitivity reactions to metronidazole.

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Background: Hypersensitivity reactions to metronidazole are infrequently described. However, we believe that such reactions are increasing due to growing use of the drug for the treatment of amebiasis and anaerobe infections combined with other antibiotics. The present study assesses the need for oral provocation in patients with probable hypersensitivity reactions to metronidazole. Methods: We performed cutaneous prick tests with spiramycin and metronidazole as well as epicutaneous tests with metronidazole at different concentrations in four patients with cutaneous reactions to Rhodogil® (metronidazole plus spiramicyn). Controlled oral challenges were then carried out with placebo using erythromycin, spiramycin and metronidazole except in the last patient due to a positive prick test. Results: Only one patient showed a positive metronidazole prick test. The epicutaneous tests were negative. All patients tolerated erythromycin and spiramycin up to therapeutic doses. Oral provocation with metronidazole proved positive, the first patient presenting a delayed exanthema and the other two early erythema and itching. Conclusions: We present four cases of cutaneous exanthemas caused by metronidazole (two early and two delayed) and probably mediated by an immune mechanism which we have only been able to demonstrate in one case. Taking into account the low sensitivity of the cutaneous tests (prick tests and epicutaneous tests), oral provocation must be considered the "gold standard" for establishing the diagnosis in many cases of hypersensitivity reactions to metronidazole

Antecedentes: Las reacciones de hipersensibilidad por metronidazol descritas no son frecuentes. Sin embargo, creemos que están aumentando debido a su mayor uso para el tratamiento de amebiasis e infecciones por anaerobios combinado con otros antibióticos. Nuestro objetivo fue valorar la necesidad de la provocación oral en pacientes con probables reacciones de hipersensibilidad por metronidazol. Métodos: Se realizaron pruebas cutáneas en prick con espiramicina y metronidazol así como pruebas epicutáneas con éste último a distintas concentraciones en cuatro pacientes que consultaron por reacciones cutáneas con Rhodogil® (metronidazol más espiramicina. A continuación se llevaron a cabo provocaciones orales controladas con placebo con eritromicina, espiramicina y metronidazol. Resultados: El prick sólo fue positivo para metronidazol en uno de los casos. Las pruebas epicutáneas fueron negativas. Todos los pacientes toleraron la eritromicina y espiramicina hasta dosis terapeúticas. La provocación oral con metronidazol fue positiva (excepto en el último paciente por la positividad del prick), presentando el primer paciente un exantema tardío y los otros dos eritema y prurito de forma precoz. Conclusiones: Presentamos cuatro casos de exantemas cutáneos por metronidazol (dos precoces y dos tardíos) probablemente mediados por un mecanismo inmunológico que sólo hemos podido demostrar en uno de ellos. Teniendo en cuenta la baja sensibilidad de las pruebas cutáneas, tanto en prick como epicutáneas, la provocación oral debe considerarse como el “gold standard” necesario para llegar al diagnóstico de muchos casos de reacciones de hipersensibilidad por metronidazol

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Antibiotics may impair the development and expression of specific or nonspecific immune responses. Prophylactic administration of antibacterial antibiotics is widely used in ICUs. We studied the immunosuppressive activities of cefotaxime, chloramphenicol, gentamicin, metronidazole, and rifamycin as a function of time after the administration of these drugs to ICU patients, finding that the last 4 drugs had an immunosuppressive activity detectable up to 8 h by a mixed lymphocyte reaction. When these antimicrobial agents were added to normal pooled plasma in concentrations similar to those obtained in vivo, a similar degree of inhibition was observed.

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The effect on cell-mediated immunity of two hypoxic cell radiosensitizers, metronidazole and misonidazole, was examined. Immunocompetence was assayed by measuring delayed hypersensitivity reactions in mice sensitized on the abdomen with 2,4-dinitro-1-fluorobenzene (DNFB) and subsequently challenged on the ears with DNFB. Single and fractionated treatments with misonidazole or metronidazole were found to suppress delayed hypersensitivity reactions to DNFB. This finding is in agreement with other data in the literature which show that many imidazoles, including nitroimidazoles, inhibit aspects of the cell-mediated immune response in animals and man. The potential immunosuppressive effects of nitroheterocyclic radiosensitizers should be considered when these agents are evaluated in the laboratory or used in the clinic.

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