Literatur zum Vortrag
1: Cochrane Database Syst Rev 2002;(1):CD001090
Update of:
Cochrane Database Syst Rev. 2001;(2):CD001090.
Intravenous immunoglobulin for treating sepsis and septic shock.
Alejandria MM, Lansang MA, Dans LF, Mantaring JB.
Clinical Epidemiology Unit, University of the Philippines Manila, College of Medicine, 547 P. Gil St., Ermita, Manila, Philippines, 1000. mlansang@pacific.net.ph
BACKGROUND: Death from severe sepsis and septic shock is common, and researchers have explored whether antibodies to the endotoxins in some bacteria reduces mortality. OBJECTIVES: To estimate the effects of intravenous immunoglobulin (IVIG) in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized register up to November 2001; the Cochrane Controlled Trials Register, The Cochrane Library issue 4, 2001; MEDLINE 1966 to November 2001; and EMBASE 1988 to September 2001. We contacted investigators active in the field for unpublished data. SELECTION CRITERIA: Randomised trials comparing intravenous immunoglobulin (monoclonal or polyclonal) with placebo or no intervention, in patients with bacterial sepsis or septic shock. DATA COLLECTION AND ANALYSIS: Inclusion criteria, trial quality assessment, and data abstraction were done in duplicate. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation. MAIN RESULTS: Twenty-seven out of 55 studies met our inclusion criteria. Pooled analysis of all types of IVIG preparations revealed a significant trend toward reduction of mortality (n= 8,856; RR=0.91; 95%CI 0.86-0.96). Overall mortality was reduced in patients who received polyclonal IVIG (n=492; RR=0.64; 95% CI 0.51 to 0.80). For the two high-quality trials on polyclonal IVIG, the RR for overall mortality was 0.30, but the confidence interval was wide (95% CI 0.09 to 0.99, n=91). Mortality was not reduced among patients who received monoclonal antibodies such as anti-endotoxins (n=2,826 in 5 good-quality studies; RR=0.97; 95% CI 0.88 to 1.07) or anti-cytokines (n=4,318; RR=0.93; 95% CI 0.86 to 1.01). A few studies measured secondary outcomes (deaths from sepsis or length of hospitalisation) but no differences in the intervention and control groups were identified except among those who received polyclonal IVIG, where sepsis-related mortality was significantly reduced (n=161; RR=0.35; 95% CI 0.18 to 0.69). REVIEWER'S CONCLUSIONS: Polyclonal IVIG significantly reduced mortality and and is a promising adjuvant in the treatment of sepsis and septic shock. However, all the trials were small and the totality of the evidence is insufficient to support a robust conclusion of benefit. Adjunctive therapy with monoclonal IVIGs remains experimental.
2: Cancer 2002 Jun 15;94(12):3230-46
Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials.
Bow EJ, Laverdiere M, Lussier N, Rotstein C, Cheang MS, Ioannou S.
Department of Internal Medicine, the University of Manitoba and CancerCare Manitoba, Winnipeg, Manitoba, Canada. ebow@hsc.mb.ca
BACKGROUND: The overall clinical efficacy of the azoles antifungal agents and low-dose intravenous amphotericin B for antifungal chemoprophylaxis in patients with malignant disease who have severe neutropenia remains unclear. METHODS: Randomized-controlled trials of azoles (fluconazole, itraconazole, ketoconazole, and miconazole) or intravenous amphotericin B formulations compared with placebo/no treatment or polyene-based controls in severely neutropenic chemotherapy recipients were evaluated using meta-analytical techniques. RESULTS: Thirty-eight trials that included 7014 patients (study agents, 3515 patients; control patients, 3499 patients) were analyzed. Overall, there were reductions in the use of parenteral antifungal therapy (prophylaxis success: odds ratio [OR], 0.57; 95% confidence interval [95% CI], 0.48-0.68; relative risk reduction [RRR], 19%; number requiring treatment for this outcome [NNT], 10 patients), superficial fungal infection (OR, 0.29; 95% CI, 0.20-0.43; RRR, 61%; NNT, 12 patients), invasive fungal infection (OR, 0.44; 95% CI, 0.35-0.55; RRR, 56%; NNT, 22 patients), and fungal infection-related mortality (OR, 0.58; 95% CI, 0.41-0.82; RRR, 47%; NNT, 52 patients). Invasive aspergillosis was unaffected (OR, 1.03; 95% CI, 0.62-1.44). Although overall mortality was not reduced (OR, 0.87; 95% CI, 0.74-1.03), subgroup analyses showed reduced mortality in studies of patients who had prolonged neutropenia (OR, 0.72; 95% CI, 0.55-0.95) or who underwent hematopoietic stem cell transplantation (HSCT) (OR, 0.77; 95% CI, 0.59-0.99). The multivariate metaregression analyses identified HSCT, prolonged neutropenia, acute leukemia with prolonged neutropenia, and higher azole dose as predictors of treatment effect. CONCLUSIONS: Antifungal prophylaxis reduced morbidity, as evidenced by reductions in the use of parenteral antifungal therapy, superficial fungal infection, and invasive fungal infection, as well as reducing fungal infection-related mortality. These effects were most pronounced in patients with malignant disease who had prolonged neutropenia and HSCT recipients.
3: Clin Infect Dis 2001 Oct 15;33(8):1295-301
A multicenter, double-blind, placebo-controlled trial comparing piperacillin-tazobactam with and without amikacin as empiric therapy for febrile neutropenia.
Del Favero A, Menichetti F, Martino P, Bucaneve G, Micozzi A, Gentile G, Furno P, Russo D, D'Antonio D, Ricci P, Martino B, Mandelli F; Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Infection Program.
Istituto Medicina Interna e Scienze Oncologiche, Universita di Perugia, Perugia, Italy. delfa@unipg.it
In a prospective, multicenter, double-blind, randomized clinical trial, we compared the efficacy of piperacillin-tazobactam (4.5 g 3 times daily intravenously) plus placebo versus piperacillin-tazobactam plus amikacin (7.5 mg/kg twice daily intravenously) for the treatment of 760 febrile, adult patients with cancer with chemotherapy-induced profound (<500 neutrophils/mm3) and prolonged (>10 days) neutropenia. A total of 733 patients were assessable for efficacy of the drug regimens, and an overall successful outcome was reported in 49% (179 of 364) of the patients who received monotherapy, compared with 53% (196 of 369) of patients who received combination therapy (P=.2). Response rates were similar with both regimens, as were incidences of bacteremia and clinically documented and possible infections. In our epidemiological setting, the initial empiric combination therapy was not associated with improved outcomes when compared with initial monotherapy.
4: J Hosp Infect 2002 Oct;52(2):93-8
Pseudomonas aeruginosa outbreak in a haematology-oncology unit associated with contaminated surface cleaning equipment.
Engelhart S, Krizek L, Glasmacher A, Fischnaller E, Marklein G, Exner M.
Institute of Hygiene and Public Health, University of Bonn, Bonn, Germany. steffen.engelhart@ukb.uni-bonn.de
An outbreak of six cases of hospital-acquired Pseudomonas aeruginosa infections (two pneumonia two septicaemia, two skin/wound infection) occurred between August and September 2000 in an adult haematology-oncology unit at a tertiary-care centre. During the outbreak, hospital-acquired infection (HAI) incidence density rates rose from 29.4 to 62.3 (P < 0.05) infections per 1000 days at risk (i.e., neutropenic days). A systematic outbreak management system was actioned in accordance with a German draft guideline. Multiple samples from the patients' environment were tested for the presence of P. aeruginosa. A total of 4.5% of samples from sanitary equipment and 20.0% of samples from surface cleaning equipment were found to be contaminated with P. aeruginosa. Genotypic analysis by pulsed-field gel electrophoresis showed different patterns for all (N = 6) of the patient isolates, however, two of the patient isolates were identical in comparison with environmental isolates from cleaning equipment (four samples) and sanitary equipment (one sample). Our investigation revealed that the cleaning staff had used cleaning solution instead of disinfectants for decontamination of the patients' environment. The outbreak was terminated after re-adoption of surface disinfection, application of sterile filters on taps and shower heads, chemical disinfection of the washbasin drains, and appointment of a hospital hygiene nurse to a previously unfilled position. After institution of the control measures, HAI incidence densities decreased to pre-outbreak level. This investigation emphasizes the need to carefully evaluate cleaning and disinfection practices for patient care, particularly in neutropenic patients.
5: Lancet Infect Dis 2002 Apr;2(4):231-42
Monotherapy or aminoglycoside-containing combinations for empirical antibiotic treatment of febrile neutropenic patients: a meta-analysis.
Furno P, Bucaneve G, Del Favero A.
PF, GB, and ADF are at the Sezione di Medicina Interna e Scienze Oncologiche, Universita di Perugia, Policlinico Monteluce, Via Brunacci Brunamonti, 06122, Perugia, Italy. farmacli@unipg.it
We set out to compare the efficacy of antibiotic monotherapy with that of combination therapy including an aminoglycoside for empirical treatment of febrile neutropenic cancer patients. We did a meta-analysis of 29 randomised clinical trials pooling data from 4795 febrile episodes and a subset of 1029 bacteraemic episodes by both fixed and random effects models. Outcome measure was clinical failure of antibiotic treatment, defined as modification of the initially allocated regimen or death during treatment. In febrile episodes, the pooled odds ratio (OR) of clinical failure with monotherapy versus combination therapy was 0.88, with 95% CI from 0.78 to 0.99 by the fixed effects model, and 0.87 with 95% CI from 0.75 to 1.01 by the more conservative random effects model. For bacteraemic episodes, the pooled OR of failure with monotherapy was 0.70 (0.54 to 0.92) by the fixed effects model, and 0.72 (0.54 to 0.95) by the random effects model. We conclude that monotherapy has been as effective as aminoglycoside-containing combinations for empirical treatment of febrile neutropenia.
6: N Engl J Med 2002 Aug 8;347(6):408-15
Comment in:
N Engl J Med. 2002 Dec 19;347(25):2080-1; author reply 2080-1.
N Engl J Med. 2002 Dec 19;347(25):2080-1; author reply 2080-1.
Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.
Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B; Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group.
Departement d'Hematologie et d'Oncologie, Hopital de Hautepierre, Strasbourg, France. raoul.herbrecht@chru-strasbourg.fr
BACKGROUND: Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. METHODS: In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. RESULTS: A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). CONCLUSIONS: In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.
7: Clin Infect Dis 2001 Feb 1;32(3):358-66
Aspergillosis case-fatality rate: systematic review of the literature.
Lin SJ, Schranz J, Teutsch SM.
Department of Pharmacy Administration, University of Illinois at Chicago, Chicago, IL, USA. slin5@uic.edu
To update the case-fatality rate (CFR) associated with invasive aspergillosis according to underlying conditions, site of infection, and antifungal therapy, data were systematically reviewed and pooled from clinical trials, cohort or case-control studies, and case series of >/=10 patients with definite or probable aspergillosis. Subjects were 1941 patients described in studies published after 1995 that provided sufficient outcome data; cases included were identified by MEDLINE and EMBASE searches. The main outcome measure was the CFR. Fifty of 222 studies met the inclusion criteria. The overall CFR was 58%, and the CFR was highest for bone marrow transplant recipients (86.7%) and for patients with central nervous system or disseminated aspergillosis (88.1%). Amphotericin B deoxycholate and lipid formulations of amphotericin B failed to prevent death in one-half to two-thirds of patients. Mortality is high despite improvements in diagnosis and despite the advent of newer formulations of amphotericin B. Underlying patient conditions and the site of infection remain important prognostic factors.
8: Clin Infect Dis 2001 Sep 1;33(5):641-7
Trends in mortality due to invasive mycotic diseases in the United States, 1980-1997.
McNeil MM, Nash SL, Hajjeh RA, Phelan MA, Conn LA, Plikaytis BD, Warnock DW.
Mycotic Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. mmm2@cdc.gov
To determine national trends in mortality due to invasive mycoses, we analyzed National Center for Health Statistics multiple-cause-of-death record tapes for the years 1980 through 1997, with use of their specific codes in the International Classification of Diseases, Ninth Revision (ICD-9 codes 112.4-118 and 136.3). In the United States, of deaths in which an infectious disease was the underlying cause, those due to mycoses increased from the tenth most common in 1980 to the seventh most common in 1997. From 1980 through 1997, the annual number of deaths in which an invasive mycosis was listed on the death certificate (multiple-cause [MC] mortality) increased from 1557 to 6534. In addition, rates of MC mortality for the different mycoses varied markedly according to human immunodeficiency virus (HIV) status but were consistently higher among males, blacks, and persons > or =65 years of age. These data highlight the public health importance of mycotic diseases and emphasize the need for continuing surveillance.
9: N Engl J Med 2002 Dec 19;347(25):2020-9
Comment in:
N Engl J Med. 2002 Dec 19;347(25):2070-2.
N Engl J Med. 2003 Mar 27;348(13):1287-8; author reply 1287-8.
Comparison of caspofungin and amphotericin B for invasive candidiasis.
Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, Lupinacci R, Sable C, Kartsonis N, Perfect J; Caspofungin Invasive Candidiasis Study Group.
Neeman-ICIC and Hospital Mexico, C.C.S.S., San Jose, Costa Rica.
BACKGROUND: Caspofungin is an echinocandin agent with fungicidal activity against candida species. We performed a double-blind trial to compare caspofungin with amphotericin B deoxycholate for the primary treatment of invasive candidiasis. METHODS: We enrolled patients who had clinical evidence of infection and a positive culture for candida species from blood or another site. Patients were stratified according to the severity of disease, as indicated by the Acute Physiology and Chronic Health Evaluation (APACHE II) score, and the presence or absence of neutropenia and were randomly assigned to receive either caspofungin or amphotericin B. The study was designed to compare the efficacy of caspofungin with that of amphotericin B in patients with invasive candidiasis and in a subgroup with candidemia. RESULTS: Of the 239 patients enrolled, 224 were included in the modified intention-to-treat analysis. Base-line characteristics, including the percentage of patients with neutropenia and the mean APACHE II score, were similar in the two treatment groups. A modified intention-to-treat analysis showed that the efficacy of caspofungin was similar to that of amphotericin B, with successful outcomes in 73.4 percent of the patients treated with caspofungin and in 61.7 percent of those treated with amphotericin B (difference after adjustment for APACHE II score and neutropenic status, 12.7 percentage points; 95.6 percent confidence interval, -0.7 to 26.0). An analysis of patients who met prespecified criteria for evaluation showed that caspofungin was superior, with a favorable response in 80.7 percent of patients, as compared with 64.9 percent of those who received amphotericin B (difference, 15.4 percentage points; 95.6 percent confidence interval, 1.1 to 29.7). Caspofungin was as effective as amphotericin B in patients who had candidemia, with a favorable response in 71.7 percent and 62.8 percent of patients, respectively (difference, 10.0 percentage points; 95.0 percent confidence interval, -4.5 to 24.5). There were significantly fewer drug-related adverse events in the caspofungin group than in the amphotericin B group. CONCLUSIONS: Caspofungin is at least as effective as amphotericin B for the treatment of invasive candidiasis and, more specifically, candidemia.
10: J Antimicrob Chemother 2002 Jul;50(1):79-88
Cefepime plus amikacin versus piperacillin-tazobactam plus amikacin for initial antibiotic therapy in haematology patients with febrile neutropenia: results of an open, randomized, multicentre trial.
Sanz MA, Lopez J, Lahuerta JJ, Rovira M, Batlle M, Perez C, Vazquez L, Julia A, Palau J, Gutierrez M, Capote FJ, Ramos F, Benlloch L, Larrea L, Jarque I; Spanish PETHEMA Group.
Servicio de Hematologia, Hospital Universitario La Fe, Av. Campanar 21, 46009 Valencia, Spain. msanz@uv.es
BACKGROUND: Standard therapy for suspected infections in patients with profound neutropenia is the combination of a beta-lactam antibiotic plus an aminoglycoside. Cefepime's broad-spectrum activity makes it an option for initial empirical therapy in neutropenic patients. The aim of this study is to evaluate the efficacy and safety of cefepime plus amikacin compared with piperacillin-tazobactam plus amikacin for initial empirical treatment of fever in adult haematology patients with severe neutropenia. METHODS: In this prospective multicentre trial, 969 patients with 984 febrile neutropenic episodes were randomized to receive iv amikacin (20 mg/kg every 24 h) combined with either cefepime (2 g every 8 h) or piperacillin-tazobactam (4 g/500 mg every 6 h). Clinical response was determined at 72 h and at completion of therapy. RESULTS: Eight hundred and sixty-seven episodes were assessable for efficacy (432 cefepime, 435 piperacillin-tazobactam). The frequency of success without modification of the empirical therapy was nearly identical for cefepime plus amikacin (49%) compared with piperacillin-tazobactam plus amikacin (51%). Similar rates of success were found for microbiologically documented infection: 40% versus 39%, respectively. Antibiotic modification was necessary in 49% of cefepime and 44% of piperacillin-tazobactam patients. The overall response rate, with or without modification of the assigned treatment, was 94% in both groups. Drug-related adverse events were reported in 10% of cefepime plus amikacin versus 11% of piperacillin-tazobactam plus amikacin patients. Mortality due to infection occurred in a total of 10 patients (two cefepime, eight piperacillin-tazobactam). CONCLUSION: The empirical regimen of cefepime plus amikacin is equivalent to piperacillin-tazobactam plus amikacin in febrile adult haematology patients with severe neutropenia.
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