RESUMEN
INTRODUCTION: Trenonacog alfa (IB1001) is a recombinant factor IX (rFIX) manufactured in Chinese hamster ovary (CHO) cells. IB1001 was evaluated in a multicentre clinical trial with haemophilia B patients. AIM: The aim was to establish IB1001 pharmacokinetic non-inferiority to comparator rFIX, safety and efficacy in previously treated patients (PTPs) with haemophilia B. METHODS: Subjects were severe or moderately severe haemophilia B adult and adolescent PTPs with no history of FIX inhibitors. RESULTS: IB1001 PK non-inferiority to comparator rFIX was demonstrated through ratio of AUC0-∞ in 32 subjects. IB1001 was well tolerated in all 76 treated subjects; the most common adverse drug reaction was headache (2.6% of subjects) and there were no reports of FIX inhibitors. Transient non-inhibitory binding FIX antibodies and anti-CHO cell protein antibodies developed in 21% and 29% of subjects respectively; no safety concerns were associated with development of these antibodies. Prophylaxis (mean duration ± SD: 17.9 ± 9.6 months, mean dose: 55.5 ± 12.9 IU/kg, median 1.0 infusion per week) was effective in preventing bleeds (median annual bleed rate: 1.52, interquartile range: 0.0-3.46). One or two IB1001 infusions resolved 84% of the bleeds, while for 84% of treatments haemostatic efficacy of IB1001 was rated excellent or good. IB1001 haemostatic efficacy for all 19 major surgeries was rated adequate or better than adequate. CONCLUSIONS: IB1001 is safe and efficacious for treatment of bleeds, routine prophylaxis and perioperative management in haemophilia B patients.
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Factor IX/uso terapéutico , Hemofilia B/tratamiento farmacológico , Adolescente , Adulto , Área Bajo la Curva , Inhibidores de Factor de Coagulación Sanguínea/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Factor IX/efectos adversos , Factor IX/farmacocinética , Semivida , Cefalea/etiología , Hemofilia B/patología , Hemorragia/prevención & control , Humanos , Masculino , Curva ROC , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
Tigecycline (TGC) has demonstrated clinical efficacy and safety, in comparison with imipenem/cilastatin in phase 3 clinical trials, for complicated intra-abdominal infection (cIAI). The present study comprised a multicentre, open-label, randomized study of TGC vs. ceftriaxone plus metronidazole (CTX/MET) for the treatment of patients with cIAI. Eligible subjects were randomized (1:1) to receive either an initial dose of TGC (100 mg) followed by 50 mg every 12 h or CTX (2 g once daily) plus MET (1-2 g daily), for 4-14 days. The primary endpoint was the clinical response in the clinically evaluable (CE) population at the test of cure (TOC) assessment. Of 473 randomized subjects, 376 were CE. Among these, clinical cure rates were 70.4% (133/189) with TGC vs. 74.3% (139/187) with CTX/MET (95% CI -13.1 to 5.1; p 0.009 for non-inferiority). Clinical cure rates for subjects with Acute Physiological and Chronic Health Evaluation II scores > or =10 were 56.8% (21/37) with TGC vs. 58.3% (21/36) with CTX/MET. The microbiologic response was similar between the two treatment arms, with microbiological eradication at TOC achieved in 68.1% (94/138) of TGC-treated subjects and 71.5% (98/137) of CTX/MET-treated subjects. (The most frequently reported adverse events (AEs) for both treatment arms were nausea (TGC, 38.6% vs CTX/MET, 27.7%) and vomiting (TGC, 23.3% vs CTX/MET, 17.7%). Overall discontinuation rates as a result of an AE were 8.9% and 4.8% in TGC- and comparator-treated subjects, respectively. The results obtained in the present study demonstrate that TGC monotherapy is non-inferior to a combination regimen of CTX/MET with respect to treating subjects with cIAI.
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Abdomen/microbiología , Antiinfecciosos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Ceftriaxona/administración & dosificación , Enfermedades Gastrointestinales/tratamiento farmacológico , Metronidazol/administración & dosificación , Minociclina/análogos & derivados , Antiinfecciosos/efectos adversos , Bacterias/aislamiento & purificación , Ceftriaxona/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Metronidazol/efectos adversos , Persona de Mediana Edad , Minociclina/administración & dosificación , Minociclina/efectos adversos , Tigeciclina , Resultado del TratamientoRESUMEN
Patients with intra-abdominal infections differ with regard to the type of infection and the severity of illness. However, the impact of these factors, together with differences in drug exposure, on clinical response is not well understood. Using phase 2 and 3 data for patients with complicated intra-abdominal infections, the relative importance of tigecycline exposure, host factors, and disease factors, alone or in combination, for the probability of clinical response was examined. Patients with complicated intra-abdominal infections who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for 5 to 14 days and who had adequate clinical, pharmacokinetic, and response data were evaluated. Multivariable logistic regression was used to identify factors associated with clinical response. A final multivariable logistic regression model demonstrated six factors based on 123 patients to be predictive of clinical success: a weight of <94 kg (P = 0.026), the absence of Pseudomonas aeruginosa in baseline cultures (P = 0.021), an APACHE II score of <13 (P = 0.029), non-Hispanic race (P = 0.005), complicated appendicitis or cholecystitis (P = 0.004), and a ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC ratio) of > or =3.1 (P = 0.003). The average model-predicted probability of clinical success when one unfavorable factor was present was 0.940. This probability was lower (0.855) when the AUC/MIC ratio was < 3.1 and the remaining five factors were set to the favorable condition. The average model-predicted probability of clinical success in the presence of two unfavorable factors was 0.594. These findings demonstrated the impact of individual and multiple factors on clinical response in the context of drug exposure.
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Cavidad Abdominal/microbiología , Antibacterianos , Bacterias Anaerobias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Enterobacteriaceae/efectos de los fármacos , Minociclina/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Área Bajo la Curva , Infecciones Bacterianas/microbiología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Minociclina/administración & dosificación , Minociclina/farmacología , Minociclina/uso terapéutico , Valor Predictivo de las Pruebas , Tigeciclina , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are causing serious nosocomial infections. Tigecycline was evaluated in hospitalized patients with MRSA or VRE infection. PATIENTS AND METHODS: A randomized (3:1), double-blind, multicentre, Phase 3 study compared the safety and efficacy of tigecycline with vancomycin or linezolid in hospitalized patients with MRSA or VRE infection, respectively. Patients were treated for 7-28 days and the test-of-cure (TOC) assessment was made 12-37 days after the last dose. The primary efficacy endpoint was the clinical response (cure, failure and indeterminate) in the co-primary, microbiologically evaluable (ME) and microbiologically modified intent-to-treat (m-mITT) populations at the TOC assessment. RESULTS: For MRSA infection, clinical cure rates in the ME population (n = 117) were 81.4% (70 of 86 patients) with tigecycline and 83.9% (26 of 31 patients) with vancomycin. In the m-mITT population (n = 133), clinical cure occurred in 75 of 100 tigecycline-treated patients (75.0%) and in 27 of 33 vancomycin-treated patients (81.8%). In patients with complicated skin and skin structure infections caused by MRSA, cure rates were similar with tigecycline or vancomycin (86.4% versus 86.9% in ME population; and 78.6% versus 87.0% in m-mITT population). In patients with MRSA infection, nausea or vomiting occurred more frequently with tigecycline than with vancomycin (41.0% versus 17.9%); most cases were mild, with only three patients discontinuing treatment. In patients with VRE (total enrollment, 15), 3 of 3 and 3 of 8 patients in the ME and m-mITT populations, respectively, were cured by tigecycline, compared with 2 of 3 patients in the ME and m-mITT populations treated with linezolid. CONCLUSIONS: Tigecycline is safe and effective in hospitalized patients with serious infection caused by MRSA. There were too few cases of VRE to draw any conclusions.
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Antibacterianos/efectos adversos , Antibacterianos/farmacología , Enterococcus/efectos de los fármacos , Infecciones por Bacterias Grampositivas/microbiología , Resistencia a la Meticilina , Minociclina/análogos & derivados , Staphylococcus aureus/efectos de los fármacos , Resistencia a la Vancomicina , Acetamidas/efectos adversos , Acetamidas/farmacología , Anciano , Infección Hospitalaria/microbiología , Método Doble Ciego , Femenino , Hospitalización , Humanos , Linezolid , Masculino , Persona de Mediana Edad , Minociclina/efectos adversos , Minociclina/farmacología , Oxazolidinonas/efectos adversos , Oxazolidinonas/farmacología , Tigeciclina , Resultado del Tratamiento , Vancomicina/efectos adversos , Vancomicina/farmacologíaRESUMEN
Exposure-response analyses were performed to test the microbiological and clinical efficacies of tigecycline in complicated intra-abdominal infections where Escherichia coli and Bacteroides fragilis are the predominant pathogens. Data from evaluable patients enrolled in three clinical trials were pooled. Patients received intravenous tigecycline (100-mg loading dose followed by 50 mg every 12 h or 50-mg loading dose followed by 25 mg every 12 h). At the test-of-cure visit, microbiological and clinical responses were evaluated. Patients were prospectively classified into cohorts based on infection with a baseline pathogen(s): E. coli only (cohort 1), other mono- or polymicrobial Enterobacteriaceae (cohort 2), at least one Enterobacteriaceae pathogen plus an anaerobe(s) (cohort 3), at least one Enterobacteriaceae pathogen plus a gram-positive pathogen(s) (cohort 4), and all other pathogens (cohort 5). The cohorts were prospectively combined to increase sample size. Logistic regression was used to evaluate ratio of steady-state 24-hour area under the concentration-time curve (AUC) to MIC as a response predictor, and classification-and-regression-tree (CART) analyses were utilized to determine AUC/MIC breakpoints. Analysis began with cohorts 1, 2, and 3 pooled, which included 71 patients, with 106 pathogens. The small sample size precluded evaluation of cohorts 1 (34 patients, 35 E. coli pathogens) and 2 (16 patients, 24 Enterobacteriaceae). CART analyses identified a significant AUC/MIC breakpoint of 6.96 for microbiological and clinical responses (P values of 0.0004 and 0.399, respectively). The continuous AUC/MIC ratio was also borderline predictive of microbiological response (P = 0.0568). Cohort 4 (21 patients, 50 pathogens) was evaluated separately; however, an exposure-response relationship was not detected; cohort 5 (31 patients, 60 pathogens) was not evaluated. The prospective approach of creating homogenous populations of pathogens was critical for identifying exposure-response relationships in complicated intra-abdominal infections.
Asunto(s)
Cavidad Abdominal/microbiología , Antibacterianos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Minociclina/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Área Bajo la Curva , Bacterias Anaerobias/efectos de los fármacos , Método Doble Ciego , Femenino , Bacterias Gramnegativas/clasificación , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/microbiología , Bacterias Grampositivas/clasificación , Bacterias Grampositivas/efectos de los fármacos , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana/normas , Persona de Mediana Edad , Minociclina/administración & dosificación , Minociclina/farmacocinética , Minociclina/uso terapéutico , Tigeciclina , Resultado del TratamientoRESUMEN
The polymicrobial nature of complicated intra-abdominal infections makes these infections particularly challenging to treat. The initial selection of antimicrobial therapy is therefore extremely important. Inappropriate empiric antimicrobial therapy has been shown to delay clinical resolution, increase length of hospital stay, and increase the risk of mortality. In addition, the increasing frequency with which resistant isolates (e.g., extended spectrum beta-lactamases [ESBLs]) are recovered from patients mandates that empiric antimicrobial therapy covers these difficult-to-treat organisms. Here, we assessed the efficacy of a new antimicrobial agent, tigecycline. This is a combined analysis of data from the European sites that participated in two Phase III, double-blind trials to evaluate the efficacy and safety of tigecycline, versus that of imipenem/cilastatin, in adults with complicated intra-abdominal infections. Patients received either tigecycline (initial dose of 100 mg, followed by 50 mg intravenously every 12 hours) or imipenem/cilastatin (500/500 mg intravenously every 6 hours) for 5-14 days. The primary end point was the clinical response at the test-of-cure visit (12-44 days after therapy) in the co-primary microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations. For the ME group, clinical cure rates at the test-of-cure visit were 92.4% (219/237) for tigecycline versus 88.8% (198/223) for imipenem/cilastatin (95% CI = -2.2, 9.4). Clinical cure rates for the mmITT populations were 87.3% (247/283) for tigecycline versus 83.5% (228/273) for imipenem/cilastatin (95% CI = -2.5, 10.0) at the test-of-cure visit. Pretherapy in vitro activity against baseline isolates for tigecycline and imipenem/cilastatin were also determined. The mean MIC(90) for tigecycline against the most commonly isolated aerobes and anaerobes was < or =2.0 microg/mL. No pretherapy isolates displayed resistance to tigecycline based on the breakpoints used. Bacterial susceptibilities to tigecycline appeared to be consistent with clinical responses. Most commonly reported treatment emergent adverse events for tigecycline and imipenem/cilastatin were nausea (14.7% and 11.8%, respectively, p = 0.267) and vomiting (10.7% and 7.3%, respectively p = 0.146). This combined analysis demonstrates that tigecycline is safe and effective for the treatment of complicated intra-abdominal infections, and reflects the findings of the global population.
Asunto(s)
Absceso Abdominal/tratamiento farmacológico , Antibacterianos/uso terapéutico , Minociclina/análogos & derivados , Absceso Abdominal/microbiología , Antibacterianos/efectos adversos , Cilastatina/uso terapéutico , Combinación Cilastatina e Imipenem , Método Doble Ciego , Combinación de Medicamentos , Quimioterapia Combinada , Europa (Continente) , Femenino , Humanos , Imipenem/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Minociclina/efectos adversos , Minociclina/uso terapéutico , Seguridad , Tigeciclina , Resultado del TratamientoRESUMEN
Exposure-response analyses were performed for the microbiological and clinical efficacy of tigecycline in the treatment of complicated skin and skin-structure infections, where Staphylococcus aureus and streptococci are the predominant pathogens. A prospective method was developed to create homogeneous patient populations for PK-PD analyses. Evaluable patients from three clinical trials were pooled for analysis. Patients received a tigecycline 100-mg loading dose/50 mg every 12 h or a 50-mg loading dose/25 mg every 12 h. At the test-of-cure visit, microbiologic and clinical responses were evaluated. Patients were prospectively evaluated and classified into cohorts based on baseline pathogens: S. aureus only (cohort 1), monomicrobial S. aureus or streptococci (cohort 2), two gram-positive pathogens (cohort 3), polymicrobial (cohort 4), or other monomicrobial infections (cohort 5). A prospective procedure for combining cohorts was used to increase the sample size. Logistic regression evaluated steady-state 24-h area under the concentration-time curve (AUC(24))/MIC ratio as a predictor of response, and classification and regression tree (CART) analyses were utilized to determine AUC/MIC breakpoints. Analysis began with pooled cohorts 2 and 3, the focus of these analyses, and included 35 patients with 40 S. aureus and/or streptococcal pathogens. CART analyses identified a significant AUC/MIC breakpoint of 17.9 (P = 0.0001 for microbiological response and P = 0.0376 for clinical response). The continuous AUC/MIC ratio was predictive of microbiological response based on sample size (P = 0.0563). Analysis of all pathogens combined decreased the ability to detect exposure-response relationships. The prospective approach of creating homogeneous populations based on S. aureus and streptococci pathogens was critical for identifying exposure-response relationships.
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Antibacterianos , Minociclina/análogos & derivados , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Streptococcus/efectos de los fármacos , Adulto , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Área Bajo la Curva , Método Doble Ciego , Femenino , Humanos , Modelos Logísticos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Minociclina/administración & dosificación , Minociclina/farmacocinética , Minociclina/uso terapéutico , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/microbiología , Streptococcus/clasificación , Tigeciclina , Resultado del TratamientoRESUMEN
This study identified 37 intensive care unit (ICU) patients with gram-negative rod (GNR) bacteraemia. The sources, causative organisms and mortality of gram-negative bacteraemia were consistent with historical series. Antibiotic resistance among well-described species with a propensity for antimicrobial resistance was the most common reason for ineffective antibiotic administration. This study emphasizes the importance of antibiotic resistance in antimicrobial selection and the power of Acute Physiology and Chronic Health Evaluation criteria for predicting patient mortality.
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Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/mortalidad , Unidades de Cuidados Intensivos , APACHE , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Femenino , Bacterias Gramnegativas/clasificación , Bacterias Gramnegativas/patogenicidad , Infecciones por Bacterias Gramnegativas/clasificación , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Two phase 3, double-blind studies in hospitalized adults with complicated skin and skin-structure infections (cSSSI) determined the safety and efficacy of tigecycline versus that of vancomycin-aztreonam. Patients received tigecycline (100 mg, followed by 50 mg intravenously twice daily) or vancomycin (1 g intravenously twice daily) plus aztreonam (2 g intravenously twice daily) for up to 14 days. Populations were as follows: 1116 patients (566 treated with tigecycline, and 550 treated with vancomycin-aztreonam) constituted the modified intent-to-treat (mITT) population, 1057 patients (538 treated with tigecycline, and 519 treated with vancomycin-aztreonam) constituted the clinical mITT (c-mITT) population, and 833 patients (422 treated with tigecycline, and 411 treated with vancomycin-aztreonam) constituted the clinically evaluable population. Clinical responses to tigecycline and vancomycin-aztreonam at test-of-cure were similar: c-mITT, 79.7% (95% confidence interval [CI], 76.1%-83.1%) versus 81.9% (95% CI, 78.3%-85.1%) (P = .4183); and clinically evaluable, 86.5% (95% CI, 82.9%-89.6%) versus 88.6% (95% CI, 85.1%-91.5%) (P = .4233). Adverse events were similar, with increased nausea and vomiting in the tigecycline group and increased rash and elevated hepatic aminotransferase levels in the vancomycin-aztreonam group. Tigecycline monotherapy is as safe and efficacious as the vancomycin-aztreonam combination in treating patients with cSSSI.
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Antibacterianos/uso terapéutico , Aztreonam/uso terapéutico , Minociclina/análogos & derivados , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Vancomicina/uso terapéutico , Adulto , Anciano , Antibacterianos/efectos adversos , Aztreonam/efectos adversos , Bacterias/efectos de los fármacos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Minociclina/efectos adversos , Minociclina/uso terapéutico , Distribución Aleatoria , Enfermedades Cutáneas Bacterianas/microbiología , Tigeciclina , Vancomicina/efectos adversosRESUMEN
A significant percentage of human immunodeficiency virus type 1 (HIV-1)-infected persons treated with highly active antiretroviral therapy (HAART) will develop plasma HIV-1-specific virion RNA levels <50 copies/mL. HIV-1-infected persons receiving virally suppressive HAART were studied with a viral outgrowth assay of the patients' peripheral blood mononuclear cells (PBMC), and a quantitative polymerase chain reaction assay was used to analyze HIV-1 2-long terminal repeat (2-LTR) circular DNA in PBMC, which indicates new HIV-1 infections of cells in vivo. Viral outgrowth in vitro correlated inversely with the level of peripheral blood CD4(+) T lymphocytes. Detection and quantitation of 2-LTR circular DNA correlated strongly with viral outgrowth patterns and inversely with CD4(+) T lymphocyte counts. Relevant subgroups of HIV-1-infected subjects on suppressive HAART with residual viral disease and reservoirs can now be stratified.
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ADN Viral/análisis , Infecciones por VIH/virología , VIH-1/genética , Provirus/genética , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Estudios de Cohortes , ADN Complementario/análisis , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Duplicado del Terminal Largo de VIH/genética , VIH-1/patogenicidad , Humanos , Masculino , Factores de Tiempo , Replicación ViralRESUMEN
PURPOSE: To review reported inflammatory reactions occurring after initiation of highly active antiretroviral therapy (HAART) in persons infected with HIV-1 and to explore the mechanisms leading to these reactions. DATA SOURCES: MEDLINE search of biomedical literature reporting inflammatory reactions after HAART. Bibliographies of retrieved reports were also reviewed. STUDY SELECTION: Articles describing patients infected with HIV-1 who had immunologic and virologic responses to HAART and subsequently developed inflammatory reactions. DATA EXTRACTION: Data on the immune status, clinical characteristics, and therapeutic management of patients who were seropositive for HIV-1 and had inflammatory reactions after HAART. DATA SYNTHESIS: Inflammatory reactions involving opportunistic infections, AIDS-associated malignant conditions, and other noninfectious diseases have recently been described in patients infected with HIV-1. These conditions often appeared shortly after the introduction of HAART and were associated with pronounced reductions in plasma HIV-1 viral load and increases in CD4(+) T-lymphocyte counts. Clinical presentation was often atypical of that in patients with untreated HIV-1 infection, probably because of restored immunity. Most cases improved despite continuation of HAART, although some patients required anti-inflammatory drugs or specific antimicrobial agents. CONCLUSIONS: Clinicians caring for patients who are infected with HIV-1 and receiving HAART must be aware of this new and diverse clinical syndrome. As more HAART recipients are studied, new presentations will probably be observed.
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Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1 , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Enfermedades Autoinmunes/diagnóstico , Recuento de Linfocito CD4 , Quimioterapia Combinada , Infecciones por VIH/virología , VIH-1/genética , Humanos , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Neoplasias/diagnóstico , ARN Viral/sangre , Carga ViralRESUMEN
It has been previously reported that the most common cause of peritonitis in patients undergoing chronic ambulatory peritoneal dialysis (CAPD) is infection by a single gram-positive bacterial species. Polymicrobial bacterial infections are identified that may be secondary to bowel perforation. In 20% of cases bacterial cultures are negative. Although cultures may be negative when infection is due to a fastidious organism, when antibiotic therapy has been administered, and in cases of chemical peritonitis, a viral etiology should also be considered. We report the first documented case of herpes simplex peritonitis, which involved a 60-year-old female undergoing CAPD. Viral peritonitis may be an important form of peritonitis that has been previously unrecognized and should be considered in the differential diagnosis.
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Herpes Simple/patología , Peritonitis/patología , Femenino , Humanos , Persona de Mediana Edad , Diálisis Peritoneal Ambulatoria Continua/efectos adversosRESUMEN
Lone pyogenic involvement of the posterior elements of the vertebrae is a rare event. We present two cases of isolated lumbar vertebral infection of the posterior elements and review 13 cases previously reported in the literature. Clinical presentation, laboratory and radiographic findings, microbiological etiology, and treatment were evaluated. Back pain, an elevated erythrocyte sedimentation rate, and computed tomography or magnetic resonance imaging were most useful in identifying the presence and extent of infection. Antibiotic therapy with or without surgical intervention was successful in all cases.
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Infecciones Bacterianas/diagnóstico , Vértebras Lumbares/microbiología , Osteomielitis/diagnóstico , Osteomielitis/microbiología , Adulto , Anciano , Sedimentación Sanguínea , Vértebras Cervicales/microbiología , Niño , Femenino , Infecciones por Bacterias Grampositivas/diagnóstico , Humanos , Lactante , Infecciones por Klebsiella/diagnóstico , Recuento de Leucocitos , Vértebras Lumbares/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteomielitis/etiología , Infecciones Neumocócicas/diagnóstico , Infecciones por Pseudomonas/diagnóstico , Radiografía , Infecciones Estafilocócicas/diagnósticoRESUMEN
Hepatic cryosurgery is a novel procedure for patients with metastatic liver disease. To date, no reviews of the infectious complications of this procedure have been published. One hundred and fifty patients underwent 158 hepatic cryosurgical procedures at Allegheny General Hospital (Pittsburgh) from November 1987 through July 1995. Gastrointestinal malignancies accounted for 93% of the underlying diagnoses. The following 12 infections were directly related to the cryosurgical procedure: hepatic abscess (six), intraperitoneal abscess (three), ascending cholangitis (two), and an intrahepatic device (Infusaid; Strato/Infusoid, Norwood, MA) infection (one). Enterococcus was the most commonly isolated organism. Seven of the 12 infections were polymicrobial. The patients who developed infections had longer hospital stays (26 days vs. 13 days) and had more days of fever (6.5 days vs. 2.3 days). than those who did not develop infections. If perioperative manipulation of the biliary tree is avoided, the infection rate in patients who undergo hepatic cryosurgery may be decreased even further. Overall, cryoablation of the liver is not related to an increased risk of infection.
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Infecciones Bacterianas/microbiología , Criocirugía/efectos adversos , Neoplasias Hepáticas/cirugía , Infección de la Herida Quirúrgica/microbiología , Factores de Edad , Anciano , Infecciones Bacterianas/epidemiología , Femenino , Neoplasias Gastrointestinales/cirugía , Humanos , Incidencia , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Pennsylvania/epidemiología , Factores de Riesgo , Infección de la Herida Quirúrgica/epidemiologíaAsunto(s)
Infecciones por Actinobacillus/tratamiento farmacológico , Aggregatibacter actinomycetemcomitans , Antiinfecciosos/uso terapéutico , Ciprofloxacina/uso terapéutico , Endocarditis Bacteriana/tratamiento farmacológico , Prótesis Valvulares Cardíacas/efectos adversos , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Administración Oral , Anciano , Aggregatibacter actinomycetemcomitans/aislamiento & purificación , Endocarditis Bacteriana/fisiopatología , Femenino , Prótesis Valvulares Cardíacas/microbiología , HumanosRESUMEN
Transmission of HIV from healthcare worker to patient has been documented in one report. Though the means of transmission in that case remains unknown, procedures that involve exposure to blood or mucous membranes are thought to carry an increased risk. Because of previous evidence of transmission of hepatitis B by cardiothoracic surgeons, they have been identified as a group known to perform exposure-prone invasive procedures with a risk of viral transmission. A retrospective review of 612 patients of a cardiothoracic surgeon who is HIV-positive was conducted in an attempt to identify any instance of viral transmission. A total of 189 patients received HIV testing and counseling. No positive test results were obtained.
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Trazado de Contacto/estadística & datos numéricos , Infecciones por VIH/transmisión , VIH-1 , Transmisión de Enfermedad Infecciosa de Profesional a Paciente/estadística & datos numéricos , Cirugía Torácica , Anticuerpos Anti-VIH/sangre , Infecciones por VIH/epidemiología , Seronegatividad para VIH , Seropositividad para VIH/epidemiología , Humanos , Pennsylvania/epidemiología , Estudios RetrospectivosRESUMEN
The in vitro activities of the DNA gyrase inhibitors ciprofloxacin, coumermycin, and novobiocin against 31 clinical isolates of Mycobacterium avium complex were studied using a microdilution technique. Minimal inhibitory concentrations (MICs) were determined in 4 days using Middlebrook 7H9 broth, and minimal bactericidal concentrations (MBCs) were determined by subculturing to Middlebrook 7H10 agar. MICs were: ciprofloxacin, 0.5-greater than 16 (mean, 4.1) micrograms/ml; novobiocin, 4-greater than 128 (mean, 54.7) micrograms/ml; and coumermycin, 2-greater than 16 (mean, 17.5) micrograms/ml. MBCs were usually more than two dilution steps higher than MICs. Checkerboard studies failed to reveal synergistic or antagonistic inhibitory activity of DNA gyrase-A and DNA gyrase-B inhibitors in vitro.
Asunto(s)
Ciprofloxacina/farmacología , Complejo Mycobacterium avium/efectos de los fármacos , Novobiocina/farmacología , Inhibidores de Topoisomerasa II , Aminocumarinas , Cumarinas/farmacología , Sinergismo Farmacológico , Inhibidores Enzimáticos/farmacología , Pruebas de Sensibilidad Microbiana , Complejo Mycobacterium avium/crecimiento & desarrolloRESUMEN
The fluoroquinolones have expanded the therapeutic options available for the treatment of genitourinary tract infections. Their ease of oral administration, favourable pharmacokinetics, low incidence of adverse reactions, and broad spectrum of in vitro activity against aerobic and facultative organisms make them especially suitable for treating bacteriuria, particularly when pathogens are resistant to other available oral agents. Their efficacy has also been established in the treatment of prostatis, gonorrhea and chancroid. They have lower in vitro activity against chlamydia, ureaplasma and anaerobes, and their role in the treatment of non-gonococcal urethritis, vaginitis and acute pelvic inflammatory disease is less well established.