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The role of antiviral prophylaxis for the prevention of posttransplant lymphoproliferative disease (PTLD) remains controversial for solid organ transplantation (SOT) recipients who are seronegative for Epstein-Barr virus (EBV) but who received organs from seropositive donors. We performed a systematic review and meta-analysis to address this issue. Two independent assessors extracted data from studies after determining patient eligibility and completing quality assessments. Overall, 31 studies were identified and included in the quantitative synthesis. Nine studies were included in the direct comparisons (total 2366 participants), and 22 were included in the indirect analysis. There was no significant difference in the rate of EBV-associated PTLD in SOT recipients among those who received prophylaxis (acyclovir, valacyclovir, ganciclovir, valganciclovir) compared with those who did not receive prophylaxis (nine studies; risk ratio 0.95, 95% confidence interval 0.58-1.54). No significant differences were noted across all types of organ transplants, age groups, or antiviral use as prophylaxis or preemptive therapy. There was no significant heterogeneity in the effect of antiviral prophylaxis on the incidence of PTLD. In conclusion, the use of antiviral prophylaxis in high-risk EBV-naive patients has no effect on the incidence of PTLD in SOT recipients.
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Antivirales/uso terapéutico , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/patogenicidad , Trastornos Linfoproliferativos/prevención & control , Trasplante de Órganos/métodos , Premedicación/métodos , Infecciones por Virus de Epstein-Barr/virología , Humanos , Trastornos Linfoproliferativos/etiología , PronósticoRESUMEN
Mucormycosis has emerged as an important cause of invasive fungal infection in patients with hematologic malignancies. Gastrointestinal mucormycosis is an unusual presentation of this invasive fungal infection, and it causes considerable morbidity and mortality. Such outcomes are due in part to a nonspecific presentation that results in delays in diagnosis and treatment. Successful treatment of gastrointestinal mucormycosis involves surgical debridement and appropriate antifungal therapy.
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OBJECTIVES: The most common mechanism of azole (itraconazole and voriconazole) resistance in Aspergillus fumigatus is a mutation at the cyp51A locus. The aim of our study was to determine the rate of cyp51A mutations in lung transplant recipients (LTR) undergoing targeted antifungal prophylaxis with 12 weeks of voriconazole. METHODS: We conducted a prospective study that included 22 LTR with A. fumigatus between October 2008 and November 2011. Of those, 10 LTR were colonized with A. fumigatus and 12 had invasive pulmonary aspergillosis. RESULTS: Four patients were found to have A. fumigatus isolates with a cyp51A mutation, two had colonization and two had invasive pulmonary aspergillosis. The remaining 18 LTR had WT cyp51A A. fumigatus isolates. All A. fumigatus isolates (except one due to mixed growth) were tested for antifungal susceptibility. A total of nine LTR were exposed to azoles prior to A. fumigatus isolation for a median duration of 249 (IQR 99-524) days. Azole exposure preceded the isolation of two mutant isolates and seven WT isolates. None of the cyp51A mutant isolates conferred phenotypic resistance to azoles. CONCLUSIONS: Targeted antifungal prophylaxis in LTR did not lead to cyp51A resistance mutations in this cohort. Data on larger cohorts who receive universal antifungal prophylaxis are needed.
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Antifúngicos/uso terapéutico , Aspergillus fumigatus/enzimología , Sistema Enzimático del Citocromo P-450/genética , Proteínas Fúngicas/genética , Trasplante de Pulmón , Tasa de Mutación , Aspergilosis Pulmonar/microbiología , Voriconazol/uso terapéutico , Aspergillus fumigatus/genética , Aspergillus fumigatus/aislamiento & purificación , Quimioprevención/métodos , Humanos , Estudios Prospectivos , Receptores de TrasplantesRESUMEN
INTRODUCTION: Bacterial infections are major causes of early morbidity and mortality after liver transplantation. Selective digestive decontamination (SDD) can be used pre-operatively for living-donor liver transplant (LD-LT), but its role in this setting remains controversial. METHODS: To evaluate this strategy, we retrospectively analyzed a cohort of consecutive LD-LTs performed in our center from March 2007 to February 2011 and compared the incidence and nature of early infectious complications, length of intensive care unit stay and hospitalization, antibiotic use, and emergence of resistant bacteria in patients with or without SDD prophylaxis. RESULTS: Of 148 LD-LTs in the study period, 111 received SDD prophylaxis while 37 did not. In a multivariate model, the independent factors associated with an increased risk of early post-transplant infections were length of postoperative mechanical ventilation (for every additional day odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.4-4.0; P = 0.002), and choledochojejunostomy (OR = 4.5, 95% CI 1.95-10.5; P < 0.001). Use of SDD did not affect the rate or distribution of infectious complications, duration of hospitalization, antibiotic use, or acquisition of resistant bacteria (OR = 3.52, 95% CI 0.43-15.17; P = 0.376). CONCLUSION: In conclusion, the use of SDD prophylaxis in LD-LT was not beneficial and should be avoided, as it offers no advantage and could potentiate the emergence of multidrug-resistant organisms.
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Antibacterianos/farmacología , Infecciones Bacterianas/prevención & control , Descontaminación/métodos , Sistema Digestivo/microbiología , Trasplante de Hígado/métodos , Donadores Vivos , Adulto , Antibacterianos/administración & dosificación , Colistina/administración & dosificación , Colistina/uso terapéutico , Quimioterapia Combinada , Femenino , Gentamicinas/administración & dosificación , Gentamicinas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Adulto JovenRESUMEN
Chronic hepatitis C virus (HCV) infection which is often a silent disease has resulted in a global epidemic. The diagnosis of hepatitis C virus often requires confirmation with molecular techniques such as the polymerase chain reaction for detection of HCV RNA. Following laboratory confirmation of the diagnosis, molecular techniques are routinely used to monitor HCV RNA levels, particularly in those undergoing treatment. Unfortunately, molecular tests are relatively expensive and their cost may be prohibitive in the developing world. Several studies have investigated the applicability of the hepatitis C core Ag (HCVcAg), as a substitute for measuring HCV RNA levels. In this review, we provide an overview of the major findings of these studies focused on the utility of measuring HCVcAg antigen levels in the clinical setting. Overall, measuring HCVcAg levels is associated with several advantages and disadvantages. It may be useful in different clinical settings for monitoring HCV patients after obtaining an initial baseline HCV RNA result.
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Hepacivirus/aislamiento & purificación , Antígenos de la Hepatitis C , Hepatitis C/diagnóstico , Animales , Hepacivirus/genética , Hepacivirus/metabolismo , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Antígenos de la Hepatitis C/genética , Antígenos de la Hepatitis C/metabolismo , Humanos , ARN Viral/genética , ARN Viral/metabolismoRESUMEN
Voriconazole is commonly used for prophylaxis and treatment of invasive aspergillosis in lung transplant recipients. However, the use of voriconazole may at times be limited by the development of hepatotoxicity. Our goal is to determine predictors of voriconazole-associated hepatotoxicity in lung transplant recipients. We conducted a single center retrospective cohort study of lung transplant recipients from 2006 to 2010 who received voriconazole therapy. We compared characteristics of patients who developed hepatotoxicity and those who did not. One hundred five lung transplant recipients received voriconazole. Hepatotoxicity occurred in 51% (54/105) of patients and lead to discontinuation in 34% (36/105). In univariate analysis, age less than 40 years, cystic fibrosis, use of azathioprine, history of liver disease and early initiation of voriconazole were associated with hepatotoxicity. In multivariable logistic regression analysis, perioperative initiation of voriconazole (within 30 days of transplantation) was independently associated with hepatotoxicity (OR 4.37, 95% CI: 1.53-12.43, p = 0.006). The five risk factors identified in the univariate analysis were used to build a K-nearest neighbor algorithm predictive model for hepatotoxicity. This model predicted hepatotoxicity with an accuracy of 70%. Voriconazole therapy initiated within the first 30 days of transplantation is associated with a greater risk of developing hepatotoxicity.
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Antifúngicos/efectos adversos , Hígado/efectos de los fármacos , Trasplante de Pulmón , Pirimidinas/efectos adversos , Triazoles/efectos adversos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Voriconazol , Adulto JovenRESUMEN
BACKGROUND: Kaposi's sarcoma (KS) is a vascular malignancy primarily involving the skin. This neoplasm occurs commonly in acquired immunodeficiency syndrome (AIDS) and post solid organ transplantation. Human herpesvirus type 8 (HHV-8) has been shown to play a causative role in AIDS-associated KS and in post renal transplantation KS. METHODS: Based on a MEDLINE search, we present a review of the current information on the epidemiology, pathogenesis, diagnosis and treatment of post-transplantation KS (PT-KS) with an emphasis on renal transplantation. RESULT: The different frequencies of PT-KS in different parts of the world seem to be related to seroprevalence of HHV-8 infection. Following renal transplantation and the administration of immunosuppressive therapy, HHV-8 may reactivate. The renal tubular epithelium is a site for HHV-8 latency. Rates of PT-KS in seropositive recipients and anti-HHV-8 mismatched recipients (donor+/recipient-) are approximately 13% and 4.6%, respectively. Additional risk factors for the development of PT-KS include skin color, country of birth, age at the time of transplantation, and different induction regimens including anti-thymocyte globulin, steroid, or anti-interleukin 2-receptor antagonists. Skin is the major site of involvement. Surprisingly, involvement of the transplanted organ has been reported to be extremely rare. Reduction in immunosuppressive therapy and switching to mammalian targets of rapamycin inhibitors, such as sirolimus, are effective treatments for PT-KS. In patients with no response to reduction in immunosuppressive therapy, systemic chemotherapy with different regimens has been reported to be successful. CONCLUSION: PT-KS in renal transplant patients is an important problem specifically in southern Europe and the Middle East. In the majority of patients, the diagnosis based on clinical suspicion is always essential. Clinicians should bear in mind that PT-KS may threaten graft function and hence result in rejection complications. Appropriate management increases patient survival.
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Herpesvirus Humano 8 , Trasplante de Riñón/efectos adversos , Sarcoma de Kaposi , Adolescente , Adulto , Niño , Preescolar , Europa (Continente) , Humanos , Terapia de Inmunosupresión/efectos adversos , Medio Oriente/epidemiología , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/epidemiología , Sarcoma de Kaposi/patología , Sarcoma de Kaposi/virologíaRESUMEN
BACKGROUND: Invasive mold infections (IMI) directly impact life expectancy, especially with delayed therapy. Among IMI, aspergillosis (IA) is more common than mucormycosis (IM), resulting in IA-targeted empirical treatment with voriconazole for suspected invasive pulmonary aspergillosis (IPA), despite IM ineffectiveness. Recently, isavuconazole was approved in Canada for IA and IM. The primary objective was to assess the cost-effectiveness of isavuconazole compared to voriconazole for suspected IPA in Canada. A secondary objective was to assess the impact of varying time horizons to address the wide spectrum of life expectancies, according to patients underlying diseases. RESEARCH DESIGN AND METHODS: A 5-year decision-tree was developed from the Canadian Ministry of Health (MoH) and societal perspectives. Efficacy parameters were extracted from SECURE/VITAL trials. Costs included treatment acquisition, hospitalization, adverse events and productivity loss. 3- and 10-year time horizon alternative scenarios and extensive sensitivity analyses were also conducted. RESULTS: From a MoH perspective, isavuconazole compared to voriconazole resulted in an incremental cost-utility ratio (ICUR) of $C30,160/QALY. 3- and10-year ICURs were also cost-effective, relative to a willingness-to-pay threshold of $C50,000/QALY. CONCLUSIONS: This study demonstrates that, in comparison to voriconazole, isavuconazole is a cost-effective strategy for the treatment of patients with suspected IPA, regardless of their life expectancy.
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Aspergilosis , Aspergilosis Pulmonar Invasiva , Antifúngicos , Aspergilosis/tratamiento farmacológico , Canadá , Análisis Costo-Beneficio , Humanos , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Nitrilos , Piridinas , Triazoles , VoriconazolRESUMEN
Background: Chemotherapy-induced T cell dysfunction, resulting from treatment of multiple myeloma (mm), enhances the risk for reactivation of latent tuberculous infection (ltbi). However, routine screening for ltbi has its limitations. The objective of the present study was to assess the number of patients treated for ltbi both before and after the introduction of a consistent tuberculin skin test (tst) screening program for patients with mm at our cancer centre. Methods: This retrospective observational study analyzed adult patients with mm treated with autologous hematopoietic stem-cell transplantation from 1 January 2013 to 31 December 2014, for whom tst was consistently performed at our cancer facility. Baseline demographic characteristics of patients who received tst testing and ltbi therapy were compared with those of a pre-intervention cohort of patients (1 January 2008 to 31 December 2009) who were not tested. Results: During the post-intervention period, 170 patients with mm had a tst. In 14 patients (8.2%) results were positive, and 11 of the 14 received ltbi therapy. Of another 12 patients with radiographic imaging changes consistent with prior granulomatous disease and negative tst results, 2 were treated. No cases of tuberculosis (tb) reactivation were noted in individuals who completed ltbi therapy. One case of active tb was diagnosed in a patient with a negative tst. In contrast, in the pre-intervention matched cohort of 170 patients, no tsts were performed, and no cases of active tb were documented. Conclusions: Patients with mm could benefit from a consistent tst testing policy coupled with subsequent ltbi therapy. However, universal testing might not be required. A targeted program combining evaluation of host risk factors, imaging findings, and screening tests might optimize ltbi diagnosis and management, and thus be effective in preventing the development of active tb in at-risk patients with mm.
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Instituciones Oncológicas/normas , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/prevención & control , Tamizaje Masivo/métodos , Mieloma Múltiple/complicaciones , Prueba de Tuberculina/métodos , Canadá , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Estudios RetrospectivosRESUMEN
OBJECTIVES: Exhaled breath condensate (EBC) is a noninvasive means of sampling the airways that has shown significant promise in the diagnosis of many disorders. There have been no reports of its usefulness in the detection of galactomannan (GM), a component of the cell wall of Aspergillus. The suitability of EBC for the detection of GM for the diagnosis of invasive aspergillosis (IA) using the Platelia Aspergillus enzyme-linked immunosorbent assay was investigated. METHODS: Prospective, cross-sectional study of lung transplant recipient and haemotologic malignancy patients at a university centre. EBC samples were compared to concomitant bronchoalveolar lavage (BAL) samples among lung transplant recipients and healthy controls. EBC was collected over 10 minutes using a refrigerated condenser according to the European Respiratory Society/American Thoracic Society recommendations, with the BAL performed immediately thereafter. RESULTS: A total of 476 EBC specimens with 444 matched BAL specimens collected from lung transplant recipients (n = 197) or haemotologic malignancy patients (n = 133) were examined. Both diluted and untreated EBC optical density (OD) values (0.0830, interquartile range (IQR) 0.0680-0.1040; and 0.1130, IQR 0.0940-0.1383), respectively, from all patients regardless of clinical syndrome were significantly higher than OD values in healthy control EBCs (0.0508, IQR 0.0597-0.0652; p < 0.0001). However, the OD index values did not correlate with the diagnosis of IA (44 samples were associated with IA). Furthermore, no significant correlation was found between EBC GM and the matched BAL specimen. CONCLUSIONS: GM is detectable in EBC; however, no correlation between OD index values and IA was noted in lung transplant recipients.
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Aspergillus/química , Líquido del Lavado Bronquioalveolar/química , Neoplasias Hematológicas/microbiología , Aspergilosis Pulmonar Invasiva/diagnóstico , Mananos/aislamiento & purificación , Anciano , Aspergillus/aislamiento & purificación , Pruebas Respiratorias , Líquido del Lavado Bronquioalveolar/microbiología , Estudios de Casos y Controles , Pared Celular/química , Estudios Transversales , Espiración , Femenino , Galactosa/análogos & derivados , Humanos , Huésped Inmunocomprometido , Aspergilosis Pulmonar Invasiva/microbiología , Trasplante de Pulmón , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: The empirical treatment of febrile, neutropenic patients with cancer requires antibacterial regimens active against both gram-positive and gram-negative pathogens. This study was performed to demonstrate the noninferiority of monotherapy with piperacillin-tazobactam, compared with cefepime. METHODS: We conducted a randomized-controlled, open-label, multicenter clinical trial among high-risk patients from 34 university-affiliated tertiary care medical centers in the United States, Canada, and Australia who were undergoing treatment for leukemia or hematopoietic stem cell transplantation and were hospitalized for empirical treatment of febrile neutropenic episodes. Patients received piperacillin-tazobactam (4.5 g every 6 h) or cefepime (2 g every 8 h) intravenously. The primary outcome was success (defined by defervescence without treatment modification) at 72 h of treatment, end of treatment, and test of cure in the modified intent-to-treat analysis. Secondary outcomes included time to defervescence, microbiological efficacy, the additional use of glycopeptide antibiotics, emergence of resistant bacteria, and safety. RESULTS: For 528 subjects (265 received piperacillin-tazobactam and 263 received cefepime), success rates were 57.7% and 48.3%, respectively (P = .04) at the 72-h time point, 39.6% and 31.6% (P = .06) at end of treatment, and 26.8% and 20.5% (P = .11) at the test-of-cure visit. The analyses demonstrated noninferiority for piperacillin-tazobactam at all time points (P< or = .0001). Treatment with piperacillin-tazobactam was independently associated with treatment success in multivariate analysis (odds ratio, 1.65; 95% confidence interval, 1.04-2.64; P = .035). Both regimens were well tolerated. CONCLUSIONS: This study demonstrates the noninferiority and safety of piperacillin-tazobactam monotherapy, compared with cefepime, for the empirical treatment of high-risk febrile neutropenic patients with cancer.
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Antibacterianos/uso terapéutico , Cefalosporinas/uso terapéutico , Fiebre/tratamiento farmacológico , Leucemia/terapia , Neutropenia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cefepima , Femenino , Fiebre/microbiología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/microbiología , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/uso terapéutico , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam , Resultado del TratamientoAsunto(s)
Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/etiología , Terapia de Inmunosupresión/métodos , Trasplante de Órganos/efectos adversos , Humanos , Inmunosupresores/administración & dosificación , Inmunología del Trasplante , Resultado del TratamientoRESUMEN
Amdinocillin in combination with another beta-lactam antibiotic (ampicillin, cephalothin, cefamandole or cefoxitin) was used to treat 25 patients with pyelonephritis (with or without bacteremia), pneumonia, bacteremia secondary to intravenous devices, and urinary tract infections (with catheter in place) due to gram-negative organisms. The combination resulted in a clinical response in 96 percent of the patients and a bacteriologic response in 100 percent at 72 hours. Few toxic effects were seen. At long-term follow-up, relapse occurred in three of 10 patients with pyelonephritis who were treated with a combination regimen and completed their course of antimicrobial therapy with a beta-lactam antibiotic. Reinfection occurred in one patient who had a urinary tract infection with a catheter in place. In vitro testing showed that the cefamandole-amdinocillin combination most frequently produced synergy against the strains of Escherichia coli isolated. Synergy with the antibiotic combinations was also seen against strains of Klebsiella pneumoniae. It was difficult to correlate the in vitro test results with the in vivo therapeutic effect of these antibiotic combinations.
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Amdinocilina/administración & dosificación , Antibacterianos/administración & dosificación , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Klebsiella/tratamiento farmacológico , Ácido Penicilánico/administración & dosificación , Adolescente , Adulto , Anciano , Amdinocilina/efectos adversos , Antibacterianos/efectos adversos , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Humanos , Inyecciones Intravenosas , Klebsiella pneumoniae , Masculino , Persona de Mediana EdadRESUMEN
The double beta-lactam combination of cefoperazone plus piperacillin was compared with an aminoglycoside-containing regimen of mezlocillin plus tobramycin in a prospective, randomized trial of empiric therapy for febrile neutropenic patients (neutrophils no more than 1,000/mm3). Thirty febrile episodes were treated with cefoperazone plus piperacillin and mezlocillin plus tobramycin, respectively. There was no significant difference between the two groups with respect to age, sex, pretherapy neutrophil count, and mean duration of therapy. The majority of patients had neutrophil counts of no more than 200/mm3 at the initiation of therapy. Only microbiologically and clinically documented infections were evaluated for efficacy. The cefoperazone plus piperacillin regimen appeared to have a comparable response rate with the mezlocillin plus tobramycin regimen (20 of 24 patients [83 percent] versus 16 of 23 patients [70 percent]). Gram-positive micro-organisms were seen predominantly in this study, with the cefoperazone plus piperacillin regimen achieving a bacteriologic response in 84 percent, as opposed to 60 percent for those organisms treated with the mezlocillin plus tobramycin regimen. Neither regimen was totally effective against coagulase-negative staphylococci. Eight superinfections occurred in the cefoperazone plus piperacillin arm, whereas 11 superinfections occurred in the mezlocillin plus tobramycin arm. Although fungal superinfections were most common, the number of gram-positive superinfections in the mezlocillin plus tobramycin arm exceeded those seen in the cefoperazone plus piperacillin arm. The incidence of antibiotic-related side effects was similar in the two groups. Hypokalemia was most frequently seen. Both skin rashes and nephrotoxicity were more common with mezlocillin plus tobramycin. Cefoperazone plus piperacillin was found to be effective empiric therapy in febrile neutropenic patients. This double beta-lactam combination may be particularly useful for patients who have or are at high risk for the development of renal insufficiency.
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Agranulocitosis/complicaciones , Antibacterianos/administración & dosificación , Fiebre/complicaciones , Neutropenia/complicaciones , Tobramicina/administración & dosificación , Adolescente , Adulto , Anciano , Antibacterianos/efectos adversos , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Cefoperazona/administración & dosificación , Cefoperazona/efectos adversos , Ensayos Clínicos como Asunto , Quimioterapia Combinada , Femenino , Humanos , Masculino , Mezlocilina/administración & dosificación , Mezlocilina/efectos adversos , Persona de Mediana Edad , Piperacilina/administración & dosificación , Piperacilina/efectos adversos , Estudios Prospectivos , Distribución Aleatoria , Tobramicina/efectos adversosRESUMEN
Methicillin-resistant coagulase-negative staphylococci have become increasingly responsible for febrile episodes in cancer patients, often necessitating the addition of vancomycin to an aminoglycoside-containing broad-spectrum antibiotic regimen. A total of 229 courses of antibiotic therapy in 229 patients were evaluated for nephrotoxicity associated with the administration of an aminoglycoside and/or vancomycin. The incidence of nephrotoxicity observed in patients administered an aminoglycoside (Group A) was 18 percent; vancomycin (Group B) 15 percent; and an aminoglycoside concurrently with vancomycin (Group C) 15 percent. The following pharmacokinetic/dosing factors were significantly associated with increased nephrotoxicity in the groups: baseline serum creatinine level, mean daily dose during the first three days of therapy (Group B), and elevated serum trough aminoglycoside or vancomycin concentrations (2 micrograms/ml or more or 10 micrograms/ml or more, respectively). No cumulative nephrotoxicity was demonstrated with the concurrent administration of vancomycin and an aminoglycoside. A higher incidence of nephrotoxicity was seen in Group C (42 percent) and Group B (27 percent) patients, in whom trough serum vancomycin concentrations were 10 micrograms/ml or more.
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Antibacterianos/administración & dosificación , Riñón/efectos de los fármacos , Neoplasias/sangre , Infecciones Estafilocócicas/sangre , Vancomicina/administración & dosificación , Aminoglicósidos , Antibacterianos/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico , Vancomicina/efectos adversosRESUMEN
Choice of antibiotic therapy for the management of infection in the neutropenic patient continues to challenge the clinician. The shift toward gram-positive organisms and the continuing need to provide gram-negative coverage demands the use of an agent or agents that provide coverage for the spectrum of potential infecting organisms. Cefepime is an extended-spectrum fourth-generation cephalosporin that has good activity against gram-positive and gram-negative organisms; in addition, it resists degradation by Bush group 1 beta-lactamases. These properties make this agent a promising candidate for empiric therapy with febrile neutropenic patients. Data presented in this article are from febrile neutropenic cancer patients enrolled into two randomized, prospective, nonblinded comparative U.S. clinical trials. Patients were randomized to receive cefepime (2 g thrice daily) or a comparator regimen of either ceftazidime (2 g thrice daily) or piperacillin + gentamicin (3 g every 4 hours + 1.5 mg/kg every 8 hours). When indicated, vancomycin was added to the regimen. A total of 109 febrile episodes were treated with cefepime and 107 episodes were treated with the comparator regimens. Neutropenia (< or = 500 PMNs/mm3) persisted for > or = 10 days in >40% of episodes and severe neutropenia (< or = 100 PMNs/mm3) in >25%. More than 40% of the total number of episodes were documented bacterial infections. These characteristics did not differ among treatment groups. Duration of therapy was similar in both groups (median: cefepime, 9 days; comparators, 11 days). In >40% of episodes, patients received study therapy without addition of other antibacterials (cefepime, 46%; comparators, 41%). Vancomycin was added in almost half of all the episodes (cefepime, 45%; comparators, 53%). Patients became afebrile by the fourth day of study therapy in approximately 60% of episodes (cefepime, 58%; comparators, 60%). In approximately 75% of the episodes, patients had a satisfactory response at the end of therapy (cefepime, 74%; comparators, 76%); and following approximately 90% of episodes, patients survived for >30 days (cefepime, 90%; comparators, 92%). Eradication rates were similar for all pathogens for cefepime and comparator agents. There were similar numbers of superinfecting organisms in each treatment arm; most involved gram-positive organisms. These multiple measures of efficacy suggest that initial empiric cefepime monotherapy is comparable to the pooled experience with standard therapies and that antibacterial modifications occur with similar frequency for cefepime compared with standard empiric regimens.
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Cefalosporinas/uso terapéutico , Fiebre/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Cefepima , Ceftazidima/efectos adversos , Ceftazidima/uso terapéutico , Cefalosporinas/efectos adversos , Quimioterapia Combinada , Femenino , Fiebre/etiología , Gentamicinas/efectos adversos , Gentamicinas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neutropenia/etiología , Penicilinas/efectos adversos , Penicilinas/uso terapéutico , Piperacilina/efectos adversos , Piperacilina/uso terapéutico , Estudios Prospectivos , Sobreinfección/epidemiología , Vancomicina/efectos adversos , Vancomicina/uso terapéuticoRESUMEN
The incidence of invasive nosocomial aspergillosis was studied in leukemia patients at an oncology center from 1964 to 1983. A total of 97 cases of aspergillosis occurred in 1,866 patients, yielding an overall case rate of 5.2 cases per 100 patients and an incidence rate of 9.1 per 10,000 patient days. The highest incidence rate was in patients with chronic myelogenous leukemia (13.7 cases per 10,000 patient days), followed by patients with acute myelogeneous leukemia (10.6 cases per 10,000 patient days). Subdividing patients after 1978 into those receiving bone marrow transplantation and those who did not demonstrated the predisposition of transplant recipients to aspergillosis. The rates of aspergillosis among those patients who did not receive a bone marrow transplant were highest for patients with acute myelogeneous leukemia. Increases in the annual rates of aspergillosis over time coincided with the level of internal renovation activity and major construction projects upwind of patient care facilities.
Asunto(s)
Aspergilosis/epidemiología , Infección Hospitalaria/epidemiología , Leucemia Mieloide/complicaciones , Enfermedades Pulmonares Fúngicas/epidemiología , Aspergilosis/etiología , Trasplante de Médula Ósea , Estudios de Cohortes , Infección Hospitalaria/etiología , Arquitectura y Construcción de Hospitales , Humanos , Enfermedades Pulmonares Fúngicas/etiología , New York , Trasplante/efectos adversosRESUMEN
OBJECTIVE: To describe the incidence and types of first Hickman catheter-related infection (HCRI) in cancer patients and to identify indicators for catheter removal. DESIGN: Retrospective cohort study. SETTING: A regional, tertiary, referral cancer center and its supportive care university teaching hospital. PATIENTS AND METHODS: A retrospective review was conducted of 316 consecutive adult oncology patients who underwent Hickman catheter placement from 1986 to 1990 at a regional oncology center. HCRI was determined on the basis of clinical information incriminating the Hickman catheter as the source of infection. Patient characteristics and data about HCRIs (exit site cellulitis, tunnel infection with concomitant exit site cellulitis, bloodstream infection, and exit site cellulitis with bloodstream infection) were abstracted from patient medical records. Subsequently, univariate and multivariate analyses for the risk of HCRI and catheter removal were completed. RESULTS: The incidence of first HCRI was 5.98 infections per 1,000 catheter days. Overall, 156 (49%) of 316 patients developed their first HCRI prior to catheter removal. The median time to HCRI was 90 days. Male gender (P = .0004) and hematologic malignancy (P = .0001) emerged as significant risk factors for HCRI in the univariate analysis. A cox model verified that male gender (P = .02) and hematologic malignancy (P = .004) were associated with an enhanced risk of HCRI. There were 35 exit site infections (23%), three infections of the tunnel and the exit site (2%), 80 bloodstream infections (51%), and another 38 bloodstream infections with concomitant exist site infections (24%). The incidence of bloodstream infection was 3.05 per 1,000 catheter days. Gram-positive pathogens outnumbered gram-negatives and fungi, with Staphylococcus epidermidis being most common. Fifty (32%) of 156 HCRIs resulted in catheter removal. Predictors of Hickman catheter removal in the univariate analysis were bloodstream infection (P = .046) and pathogen type (P = .006). Multiple regression analysis suggested that having a gram-negative (P = .014) or fungal (P = .057) pathogen was the most important factor for catheter removal. CONCLUSIONS: These data suggest that first HCRIs occur more commonly in male patients with hematologic malignancies than in patients with solid tumors. The removal of Hickman catheters in oncology patients probably is predicated on the causative pathogen, but further investigations are necessary to delineate this issue.
Asunto(s)
Cateterismo Venoso Central/efectos adversos , Infección Hospitalaria/microbiología , Contaminación de Equipos , Neoplasias/terapia , Sepsis/microbiología , Infección de Heridas/microbiología , Adulto , Análisis de Varianza , Distribución de Chi-Cuadrado , Femenino , Enfermedades Hematológicas , Humanos , Incidencia , Leucemia , Modelos Logísticos , Linfoma , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Análisis de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVE: To evaluate the clonality of methicillin-resistant Staphylococcus aureus (MRSA) strains among hospitalized patients. SETTING: University-affiliated, 465-bed tertiary-care teaching hospital with adjacent cancer clinic in Hamilton, Ontario, Canada. DESIGN: Thirty-five colonized and 30 infected patients from January 2, 1992, through August 31, 1993, were investigated retrospectively. Analysis by restriction fragment-length polymorphisms of ribosomal RNA genes (ie, ribotyping) of 103 nosocomial isolates of MRSA from these 65 patients and of 25 selected unrelated strains was completed. Ribotyping results were compared with the phage typing data obtained prospectively during the course of prospective MRSA surveillance. RESULTS: HindIII ribotyping was more discriminating than phage typing when epidemiologically unrelated strains were differentiated by these methods (19 different ribotypes versus 14 page types; P < .005). Two early index cases were identified. Isolates from the index cases were two different strains, identified by ribotyping analysis as ribotype A (clonal group 1) and ribotype B (clonal group 2), respectively. These two ribotypes were not found when typing the unrelated control strains. Thirty-six colonized and infected patients (55%) had clonal group 1 isolates, and 20 (31%) had clonal group 2 isolates. These two clones emerged in the hospital in January and February 1992 and dominated the entire investigated period. There also were six patients with an additional clonal group (group 4) that emerged and disappeared in the second quarter of 1993. CONCLUSIONS: This study highlights the utility of ribotyping in investigating nosocomial MRSA. Three MRSA clones caused nosocomial colonization or infection in patients at this hospital. Two of these MRSA clones, once introduced, were maintained among our patients throughout the study period.
Asunto(s)
Infección Hospitalaria/microbiología , Dermatoglifia del ADN , ADN Bacteriano/genética , ADN Ribosómico/genética , Resistencia a la Meticilina , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/clasificación , Tipificación de Bacteriófagos , Infección Hospitalaria/epidemiología , Humanos , Incidencia , Ontario/epidemiología , Reproducibilidad de los Resultados , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus/genéticaRESUMEN
Nosocomial infection rates were computed for 5,031 patients at an oncology center during a 20-month period. Twelve percent of the patients developed nosocomial infections, accounting for a total of 802 infections. The overall incidence of nosocomial infections during this study period was 6.27 infections per 1,000 patient days. The highest incidence of nosocomial infections was found in patients having acute myelogenous leukemia (30.49 infections per 1,000 patient days); bone and joint cancer (27.27 infections per 1,000 patient days); and liver cancer (26.58 infections per 1,000 patient days). The respiratory tract was the most common site of infection, followed by bloodstream, surgical wound, and urinary tract infections. Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and coagulase-negative staphylococci were most frequently implicated as pathogens. The distribution of specific types of infection according to underlying malignancy was also tabulated. These data provide nosocomial infection rates, common pathogens, and sites of infection for cancer patients, thus assisting in directing appropriate therapy for these patients.