RESUMEN
Dosage recommendations for cidofovir are available for renally competent as well as impaired patients; however, there are no data for patients undergoing continuous renal replacement therapy. We determined the single-dose concentration-versus-time profile of cidofovir in a critically ill patient undergoing continuous venovenous hemofiltration (CVVH). One dose of 450 mg cidofovir (5 mg/kg) was administered intravenously due to a proven cytomegalovirus (CMV) infection and failure of first-line antiviral therapy. Additionally, 2 g of probenecid was administered orally 3 h prior to and 1 g was administered 2 h as well as 8 h after completion of the infusion. The concentrations of cidofovir in serum and ultrafiltrate were assessed by high-performance liquid chromatography. The peak serum concentration measured at 60 min postinfusion was 28.01 mg/liter at the arterial port. The trough serum level was 19.33 mg/liter at the arterial port after 24 h. The value of the area under the concentration-versus-time curve from 0 to 24 h was 543.8 mg·h/liter. The total body clearance was 2.46 ml/h/kg, and the elimination half-life time was 53.32 h. The sieving coefficient was 0.138±0.022. Total removal of the drug was 30.99% after 24 h. Because of these data, which give us a rough idea of the concentration profile of cidofovir in patients undergoing CVVH, a toxic accumulation of the drug following repeated doses may be expected. Further trials have to be done to determine the right dosage of cidofovir in patients undergoing CVVH to avoid toxic accumulation of the drug.
Asunto(s)
Antivirales/farmacocinética , Citosina/análogos & derivados , Hemofiltración , Organofosfonatos/farmacocinética , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Cidofovir , Enfermedad Crítica , Citosina/administración & dosificación , Citosina/farmacocinética , Citosina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Organofosfonatos/administración & dosificación , Organofosfonatos/uso terapéutico , Probenecid/uso terapéuticoRESUMEN
BACKGROUND: In patients with cancers of the pancreatic and biliary tract quality of life (QOL) improvement is the main treatment goal, since survival can be prolonged only marginally. Up to date, knowledge on QOL impairments throughout the entire treatment process, often including several chemotherapy lines, is scarce. Our study aimed at investigating QOL trajectories from adjuvant treatment to palliative 3rd-line therapy METHODS: Patients were included in routine electronic patient-reported outcome monitoring at Kufstein County Hospital at the time of diagnosis and assessed with the EORTC QLQ-C30 during each chemotherapy cycle. RESULTS: Eighty out of 147 patients with pancreatic cancer or cancer of the bile ducts treated at the Kufstein County Hospital, fulfilled inclusion criteria and could be included in the study (mean age 67.4 years; 53.8% women). Physical, Emotional and Cognitive Functioning, and Global QOL deteriorated across chemotherapy lines, whereas Fatigue, Pain, Dyspnoea, Sleeping Disturbances, Diarrhoea, and Taste Alterations increased. With regard to Physical Functioning, Global QOL, Fatigue, Dyspnoea, Diarrhoea and Taste Alterations, the patients receiving adjuvant or 1st-line palliative chemotherapy did not differ significantly. Most patients in 2nd- or 3rd-line chemotherapy showed significantly higher impairments and symptom burden. However, patients under 1st and 2nd-line treatment showed stable QOL trajectories, whereas 3rd-line patients perceived substantial deteriorations. CONCLUSIONS: The results suggest early palliative treatment initiation to stabilise QOL on a level as high as possible. The continuous QOL improvement during adjuvant treatment, probably reflecting post-operative recovery, may indicate that deleterious effects of adjuvant chemotherapy on QOL are highly unlikely.
Asunto(s)
Neoplasias de la Vesícula Biliar/psicología , Neoplasias Pancreáticas/psicología , Calidad de Vida , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Encuestas y CuestionariosRESUMEN
UNLABELLED: We describe two linked cases of botulinum toxin intoxication to provide the clinician with a better idea about how botulism cases may present since early diagnosis and treatment are crucial in botulism. Botulinum toxin is the strongest neurotoxin known. METHODS: We review the available literature, the compiled clinical data, and observations. RESULTS: After a slow onset of clinical signs a married couple living in Vienna presented with dysphagia, difficulties in accommodation, inability to sweat, urinary and stool retention, dizziness, and nausea. They suffered intoxication with botulinum toxin type B. Botulism is a rarely occurring disease in Austria. In the last 21 years there were only twelve reported cases. CONCLUSION: Both patients went to a general practitioner as well as several specialists before they were sent to and correctly diagnosed at our outpatient department. To avoid long delays between intoxication and diagnosis we think it is crucial to advert to the complex symptoms a nonsevere intoxication with botulinum toxin can produce, especially since intoxications have become rare occurrences in the industrialized societies due to the high quality of industrial food production.
RESUMEN
We present a case of fever, brain abscesses, and Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha (TNF-α) therapy in a 21-year-old acne inversa patient currently taking long-term dapsone. To the best of our knowledge, this is the first report describing such a case. During antimicrobial therapy, the patient developed systemic varicella infection with severe thrombocytopenia.
Asunto(s)
Anticuerpos/efectos adversos , Bacteriemia/diagnóstico , Gemella/aislamiento & purificación , Infecciones por Bacterias Grampositivas/diagnóstico , Hidradenitis Supurativa/tratamiento farmacológico , Factores Inmunológicos/efectos adversos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antiinfecciosos/administración & dosificación , Anticuerpos/administración & dosificación , Bacteriemia/complicaciones , Bacteriemia/microbiología , Absceso Encefálico/diagnóstico , Absceso Encefálico/microbiología , Dapsona/administración & dosificación , Infecciones por Bacterias Grampositivas/microbiología , Hidradenitis Supurativa/complicaciones , Humanos , Factores Inmunológicos/administración & dosificación , Masculino , Adulto JovenRESUMEN
BACKGROUND: Taste alterations (TAs) are frequently reported by chemotherapy patients. However, research on this topic is very scarce. The etiologies of TAs are not fully known and prevalences may vary across tumour types and chemotherapy regimens. The aim of the present study was to longitudinally investigate TAs in patients with breast cancer or gynaecological cancers receiving chemotherapy, and to provide expected values for TAs for these patient populations. PATIENTS AND METHODS: One hundred and nine cancer patients (32.1% gynaecological cancer, 67.9% breast cancer) receiving chemotherapy at the Department for Internal Medicine of Kufstein County Hospital were consecutively included in the study. At each visit the Quality of Life Questionnaire-Core30 and a screening scale for TAs, consisting of two validated questions taken from the European Organisation for Research and Treatment of Cancer item bank was administered. Statistical analysis was performed using mixed-effect models. RESULTS: The prevalence of TAs in breast cancer and gynaecological cancer patients receiving chemotherapy was high (76.1%). There were differences in the extent of TAs as well as in their time course across treatment groups. The lowest TAs were found in breast cancer and gynaecological cancer patients treated with gemcitabine. The highest TAs were found in breast cancer patients treated with epirubicin/docetaxel/capecitabine. The steepest increase of TAs was found in patients treated with epirubicin/docetaxel. Moreover, significant associations between TAs and appetite loss as well as fatigue were found. CONCLUSION: The results show that TAs are an issue in breast and gynaecological cancer patients receiving different chemotherapy regimens. There is a need for a more systematic investigation of TAs in chemotherapy patients in general as well as the need to address this issue in clinical practice.
Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias de la Mama/complicaciones , Neoplasias de los Genitales Femeninos/complicaciones , Calidad de Vida , Trastornos del Gusto/inducido químicamente , Trastornos del Gusto/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Humanos , Estudios Longitudinales , Persona de Mediana Edad , PronósticoRESUMEN
We report on 17 patients with influenza A H1N1v-associated Adult Respiratory Distress Syndrome who were admitted to the intensive care unit (ICU) between June 11th 2009 and August 10th 2010 (f/m: 8/9; age: median 39 (IQR 29-54) years; SAPS II: 35 (29-48)). Body mass index was 26 (24-35), 24% were overweight and 29% obese. The Charlson Comorbidity Index was 1 (0-2) and all but one patient had comorbid conditions. The median time between onset of the first symptom and admission to the ICU was 5 days (range 0-14). None of the patients had received vaccination against H1N1v. Nine patients received oseltamivir, only two of them within 48 hours of symptom onset. All patients developed severe ARDS (PaO(2)/FiO(2)-Ratio 60 (55-92); lung injury score 3.8 (3.3-4.0)), were mechanically ventilated and on vasopressor support. Fourteen patients received corticosteroids, 7 patients underwent hemofiltration, and 10 patients needed extracorporeal membrane-oxygenation (ECMO; 8 patients veno-venous, 2 patients veno-arterial), three patients Interventional Lung Assist (ILA) and two patients pump driven extracorporeal low-flow CO(2)-elimination (ECCO(2)-R). Seven of 17 patients (41%) died in the ICU (4 patients due to bleeding, 3 patients due to multi-organ failure), while all other patients survived the hospital (59%). ECMO mortality was 50%. The median ICU length-of-stay was 26 (19-44) vs. 21 (17-25) days (survivors vs. nonsurvivors), days on the ventilator were 18 (14-35) vs. 20 (17-24), and ECMO duration was 10 (8-25) vs. 13 (11-16) days, respectively (all p = n.s.). Compared to a control group of 241 adult intensive care unit patients without H1N1v, length of stay in the ICU, rate of mechanical ventilation, days on the ventilator, and TISS 28 scores were significantly higher in patients with H1N1v. The ICU survival tended to be higher in control patients (79 vs. 59%; p = 0.06). Patients with H1N1v admitted to either of our ICUs were young, overproportionally obese and almost all with existing comorbidities. All patients developed severe ARDS, which could only be treated with extracorporeal gas exchange in an unexpectedly high proportion. Patients with H1N1v had more complicated courses compared to control patients.
Asunto(s)
Enfermedades Transmisibles Emergentes/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/epidemiología , Síndrome de Dificultad Respiratoria/epidemiología , Adulto , Austria/epidemiología , Causalidad , Comorbilidad , Enfermedad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To test the time-dependent effects of rifampicin on established biofilms of Staphylococcus epidermidis isolated from patients with cardiac implant infections and catheter-related bacteremia. METHODS: Biofilms were grown in microtiter plates for 24 hours, dyed and stained with crystal violet. The mean optical density (OD) was used for quantification. The OD ratio (ODr = OD of the treated biofilm/OD of the untreated biofilm) was used to measure changes in the thickness of the biofilms over the time. Biofilms were incubated with rifampicin (0.6 mg/mL) for 1, 5, 15, 30 and 60 minutes. Unstained biofilms were sonicated and plated on Columbia agar for time-kill curves. RESULTS: The incubation of the biofilms with rifampicin led to a significant reduction of the OD of the biofilms within 1 minute (ODr baseline: 1; ODr 1 min: 0.333 ± 0.131) (p<0.001). With regard to bacterial killing, rifampicin reduced the mean log count, but viable bacteria were still grown from biofilms in 13 out of 28 isolates despite MIC values < 0.01 mg/L. CONCLUSIONS: In conclusion, our results confirm that rifampicin at a concentration of 1.2 mg/mL immediately reduces established biofilms formed by S. epidermidis although it is not bactericidal despite very low MICs at planktonic conditions.
Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Infecciones Relacionadas con Catéteres/microbiología , Infecciones Relacionadas con Prótesis/microbiología , Rifampin/farmacología , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/efectos de los fármacos , Desfibriladores Implantables/efectos adversos , Prótesis Valvulares Cardíacas/efectos adversos , Humanos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana , Marcapaso Artificial/efectos adversos , Staphylococcus epidermidis/crecimiento & desarrollo , Staphylococcus epidermidis/aislamiento & purificación , Factores de TiempoRESUMEN
BACKGROUND: Taste alterations (TAs) are a frequent but under-recognized treatment side effect in cancer patients undergoing chemotherapy (CT). CT regimens with different toxicity profiles may vary in their impact on TAs, but research on this topic is lacking. This study assesses the prevalence of TAs and their relation to sociodemographic and clinical variables, especially CT regimens. Furthermore, the association between TAs and quality of life (QOL) is investigated. PATIENTS AND METHODS: TAs and QOL data were collected longitudinally in 197 cancer patients (lung cancer, 54.3%; pancreatic cancer, 19.3%; colorectal cancer, 26.4%; age, 65.2 +/-10.4 years; male, 57.4%) who were receiving CT at the Department of Internal Medicine at Kufstein County Hospital, giving rise to a total of 1,024 assessment times. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and two additional questions taken from the EORTC item bank concerning TAs. Statistical analyses were performed using mixed-effect models. RESULTS: The study showed that the prevalence of TAs in chemotherapy patients is alarmingly high (69.9%). There were clear differences in TA scores among treatment groups: patients receiving irinotecan reported significantly more TAs than patients in other treatment groups; patients receiving a combination of gemcitabine and a platinum agent reported the lowest TAs. Additionally, significant associations between TAs and several QOL dimensions were found, especially with appetite loss and fatigue. CONCLUSION: The high prevalence of TAs and their impact on QOL in CT patients underscore the urgent need for increased attention to this side effect, both in research and in clinical practice.
Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Trastornos del Gusto/inducido químicamente , Gusto/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Calidad de VidaRESUMEN
A 64-year-old otherwise healthy patient presented with high fever, thrombocytopenia, elevated liver enzymes and an erythema on the belly. The patient remembered a tick bite four weeks ago when walking with his dog before the specific symptoms started. A meningococcal disease or hematological illness was excluded. The serological results for tick-borne diseases showed a high IgG antibody titer for Anaplasma phagocytophila. All symptoms and laboratory parameters normalized after one week of hospitalization. The patient received no treatment and recovered completely. This is the first confirmed case of human granulocytic anaplasmosis (HGA) in Eastern Austria.
Asunto(s)
Anaplasmosis/diagnóstico , Anaplasma/inmunología , Anaplasmosis/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Austria , Mordeduras y Picaduras/complicaciones , Diagnóstico Diferencial , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , GarrapatasRESUMEN
Septic-embolic diseases are life threatening; survival critically depends on rapid diagnosis. Clinically, cutaneous manifestations like Janeway lesions are infrequently occurring but highly characteristic. In contrast, histological features are not clearly defined. We report the case of a 59-year-old male patient in deteriorating general condition and fever of unknown origin with lesions suggestive for Janeway lesions. Histology showed dilated blood vessels and extravasated erythrocytes throughout the dermis. Only serial sections revealed single, deep dermal vessels occluded by fibrin thrombi. Computed tomography scan identified multiple pulmonary round masses. Blood cultures showed growth of Staphylococcus aureus and Enterococcus faecalis. The knowledge of the described subtle histological features and a clinical-pathological correlation is essential for the diagnosis of certain cases of septic-embolic conditions.
Asunto(s)
Enterococcus faecalis , Infecciones por Bacterias Gramnegativas/complicaciones , Sepsis/complicaciones , Enfermedades de la Piel/patología , Infecciones Estafilocócicas/complicaciones , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/uso terapéutico , Vasos Sanguíneos/patología , Embolia/microbiología , Embolia/patología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/patología , Humanos , Masculino , Persona de Mediana Edad , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Sepsis/patología , Piel/irrigación sanguínea , Piel/patología , Enfermedades de la Piel/etiología , Enfermedades de la Piel/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/patologíaRESUMEN
Moxifloxacin is a novel antibacterial agent that undergoes extensive metabolism in the liver to the glucuronide M1 and the sulfate M2, which are eliminated via the bile. To investigate the role of the multidrug resistance-associated protein (Mrp2) as the hepatic transport system for moxifloxacin and its conjugates, livers of Wistar and Mrp2-deficient TR- rats were perfused with moxifloxacin (10 microM) in a single-pass system. Values for the hepatic extraction ratio (E) and clearance (Cl) were insignificantly higher in TR- rats than Wistar rats (0.193+/-0.050 vs 0.245+/-0.050 for E; 6.85+/-1.96 vs 8.73+/-1.82 mL min(-1) for Cl), whereas biliary excretion and efflux into perfusate over 60 min were significantly lower in the mutant rat strain. Cumulative biliary excretion of M1, M2 and moxifloxacin was significantly reduced to 0.027%, 19.1%, and 29.6% in the TR- rats compared with Wistar rats, indicating that the biliary elimination of M1 is mediated exclusively by Mrp2, whereas that of M2 and moxifloxacin seems to depend mostly on Mrp2 and, to a smaller extent, a further unidentified canalicular transporter. Moxifloxacin stimulates bile flow by up to 11% in Wistar rats, but not in TR- rats, further supporting an efficient transport of this drug and its glucuronidated and sulfated metabolites by Mrp2. Moxifloxacin (10 microM) also reversibly inhibited the Mrp2-mediated biliary elimination of bromsulphthalein in Wistar rats by 34%, indicating competition with the elimination of Mrp2-specific substrates. In conclusion, we found that Mrp2 mediates the biliary elimination of moxifloxacin and its glucuronidated and sulfated metabolites in rats. MRP2 may therefore play a key role in the transport of moxifloxacin and its conjugates into bile in humans.
Asunto(s)
Compuestos Aza/metabolismo , Bilis/metabolismo , Hígado/metabolismo , Proteínas de Transporte de Membrana/fisiología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/fisiología , Quinolinas/metabolismo , Algoritmos , Animales , Antibacterianos/administración & dosificación , Antibacterianos/metabolismo , Antibacterianos/farmacocinética , Compuestos Aza/administración & dosificación , Compuestos Aza/farmacocinética , Disponibilidad Biológica , Fluoroquinolonas , Glucurónidos/química , Glucurónidos/metabolismo , Técnicas In Vitro , Masculino , Proteínas de Transporte de Membrana/genética , Tasa de Depuración Metabólica , Estructura Molecular , Moxifloxacino , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Perfusión/métodos , Quinolinas/administración & dosificación , Quinolinas/farmacocinética , Ratas , Ratas Mutantes , Ratas Wistar , Sulfatos/química , Sulfatos/metabolismoRESUMEN
Dengue fever is a significant health problem in most tropical regions and increasingly observed among travelers returning from tropical countries. Clinical presentation might not be typical in patients from non-endemic areas. We report 2 patients returning from South-East Asia with proven Dengue-virus infection initially presenting with "febrile diarrhea" followed by hemorrhagic skin lesions during hospitalization. Blood and stool examination remained negative for bacteria, parasites and plasmodia. Dengue fever was suspected early, mainly due to the typical course of the complete blood cell count with thrombocytopenia (19 x 10(9)/L and 86 x 10(9)/L) and leucopenia (3 x 10(9)/L and 1.8 x 10(9)/L). Both patients had a benign clinical course, which still required intensive care monitoring. Platelet inhibitors and NSAIDs should be stopped when Dengue infection (Dengue fever and Dengue hemorrhagic fever) is suspected in order to minimalize the risk of bleeding. Although presentation of the disease might not always be typical, Dengue infection has to be considered early in the course of disease by taking an in-depth history and profound physical examination.