[Show abstract][Hide abstract] ABSTRACT: Intensive chemotherapy with severe neutropenia is associated with invasive fungal infections (IFIs) leading to high mortality rates. During leukaemia induction chemotherapy, IFI often prohibited further curative treatment, thus predisposing for leukaemia relapse. Continuing myelosuppressive chemotherapy after diagnosis of IFI has become feasible with the now expanding arsenal of safe and effective antifungals. Secondary prophylaxis of IFI is widely administered, but reliable data on outcome and risk factors for recurrent IFI during subsequent chemotherapy are not available. This study determines risk factors for recurrent IFI in leukaemia patients.
From 25 European cancer centres, 166 consecutive patients with acute myelogenous leukaemia (AML) and a recent history of proven or probable pulmonary IFI were included. Patients were followed for recurrence or breakthrough IFI during the subsequent chemotherapy cycle.
Of the 166 patients included, 69 (41.6%) were female, the median age was 53 years (range 2-81) the and 3 (1.8%) were <16 years. Recurrent IFI occurred in 26 patients (15.7%). Multiple logistic regressions yielded predisposing factors: duration of neutropenia [per additional day; odds ratio (OR) 1.043, confidence interval (CI) 1.008-1.078], high-dose cytarabine (OR 3.920, CI 1.120-12.706), number of antibiotics (per antibiotic; OR 1.504, CI 1.089-2.086), partial response as outcome of prior IFI (OR 4.037, CI 1.301-12.524) and newly diagnosed AML (OR 3.823, CI 0.953-15.340). Usage of high efficiency particulate air filter appeared protective (OR 0.198, CI 0.036-1.089).
Duration of neutropenia, high-dose cytarabine, prior antibiotic therapy and a partial response to the first IFI therapy were risk factors for recurrent IFI and should be considered in AML patients with prior pulmonary IFI undergoing further chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: Autologous stem cell transplantation has augmented treatment successes. However, high-dose chemotherapy is still accompanied by dose-limiting toxicities, for example, severe mucositis. Mucosal lesions serve as portals of entry for infections. In order to reduce the oral microbial burden, we prospectively evaluated the microbiological impact of a complex regimen of mouth rinses consisting of concomitantly applied polyene antifungals, povidone-iodine, chlorhexidine, sage tea, and prophylactic ciprofloxacin and fluconazole. A total of 15 patients were enrolled into this longitudinal evaluation. Colony-forming units (CFU) were quantitated from saliva, buccal and palatinal swabs during high-dose chemotherapy and autologous stem cell transplantation. The number of CFU did not show any significant changes after initiation of the mouth rinses and the prophylactic antibiotics. The median CFU count was 268 x 10(6)/ml saliva before chemotherapy and decreased after initiation of intravenous antibiotics only. Neither prophylactic nor therapeutic antifungals significantly reduced the number of cultures positive for yeasts. Since 90% of our patients had febrile neutropenia at some time point during the observation period, the approach evaluated cannot be recommended as prophylaxis of febrile neutropenia as such.
Bone Marrow Transplantation 06/2005; 35(10):997-1001. DOI:10.1038/sj.bmt.1704933 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A case of disseminated infection with Fusarium oxysporum following chemotherapy of acute myelogenous leukemia is reported. Antifungal treatment was successful with a 13-day course of oral terbinafine 250 mg t.i.d. in combination with amphotericin B deoxycholate 1.0-1.5 mg/kg qd and subsequently intravenous liposomal amphotericin B 5 mg/kg qd. Preceding monotherapy with amphotericin B deoxycholate 1.0-1.5 mg/kg qd had not stopped the progression of infection. The combination therapy described here represents a novel approach to the treatment of Fusarium spp. in the immunocompromised host in whom Fusarium spp. are known to cause disseminated infection with high mortality.
Annals of Hematology 07/2004; 83(6):394-7. DOI:10.1007/s00277-003-0795-x · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the clinical and epidemiologic features, excess length of stay, extra costs, and mortality attributable to bloodstream infection (BSI) in neutropenic patients with hematologic malignancies.
Prospective cohort and matched case-control study.
All adult neutropenic patients with hematologic malignancies admitted to Cologne University Hospital between May 1, 1997, and April 30, 1998, were prospectively observed. Case-patients were defined as patients with nosocomial BSI; control-patients were selected among patients without BSI.
During the study period, the BSI rate in neutropenic patients was 14.3 per 100 neutropenic episodes. Eighty-four case-patients were included. Matching was successful for 96% of the cohort; 81 matched pairs were studied. The mean total length of stay was significantly longer for patients with BSI than for control-patients (37 vs 29 days; P = .002). Extra costs attributable to the infection averaged 3,200 dollars (U.S.) per patient. The crude mortality rates of case-patients and control-patients were 16% and 4%, respectively (P = .013), with an attributable mortality of 12% (odds ratio, 11). Eighty-seven percent of patients met the criteria for sepsis according to the American College of Chest Physicians/Society of Critical Care Medicine. Severe sepsis or septic shock occurred in 13% of patients and was correlated with mortality (55% vs 10% in patients without severe sepsis or septic shock; P = .01).
Nosocomial BSI in neutropenic patients is significantly associated with an excess length of hospital stay, extra costs, and excess mortality. Severe sepsis and septic shock are closely correlated with an adverse outcome.
Infection Control and Hospital Epidemiology 01/2004; 24(12):905-11. DOI:10.1086/502158 · 4.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A prospective, randomized, controlled multicenter trial was performed to evaluate the efficacy and safety of once-daily oral monotherapy with 500 mg levofloxacin in comparison with 4.5 g piperacillin/tazobactam 3 times a day in patients with low-risk febrile neutropenia. Low risk was defined by oral temperature > or = 38.5 degrees C on one occasion or > or = 38.0 degrees C twice within 24 hours and granulocytopenia < or = 500/microL for less than 10 days. The primary end point was defined as defervescence after 72 hours followed by at least 7 afebrile days. Secondary end points were overall response, time to defervescence, survival on day 30, and toxicity. Thirty-four episodes were included. Fever of unknown origin accounted for 26 (76.5%) of the episodes, microbiologically defined infection for 5 (14.7%) of the episodes, and clinically defined infection for 3 (8.8%) of the episodes. On an intent-to-treat basis, all episodes were evaluable for the primary end point. Levofloxacin and piperacillin/tazobactam were successful after 72 hours of treatment in 76.5% and 88.3% of the episodes. Overall response was achieved in 94.1% and 100% of the episodes, respectively. One inpatient in the oral treatment group died of septic shock without identification of a causative pathogen. A larger phase III trial is warranted to further evaluate the lack of inferiority of the oral monotherapy regimen versus standard intravenous therapy.
International Journal of Hematology 01/2004; 79(1):74-8. DOI:10.1007/BF02983537 · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatitis C virus (HCV) is an important cause of liver disease in human immunodeficiency virus (HIV)-infected patients.
To assess the cost-effectiveness of alternative management strategies for chronic HCV in co-infected patients with moderate hepatitis.
A state-transition model was used to simulate a cohort of HIV-infected patients with a mean CD4 cell count of 350 cells/ micro L and moderate chronic hepatitis C stratified by genotype. Strategies included interferon alfa (48 weeks), pegylated interferon alfa (48 weeks), interferon alfa and ribavirin (24 and 48 weeks), pegylated interferon alfa and ribavirin (48 weeks), and no treatment. Outcomes included life expectancy, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios.
Treatment for moderate chronic HCV with combination therapy using an interferon-based regimen reduced the incidence of cirrhosis and provided gains in quality-adjusted life expectancy ranging from 6.2 to 13.9 months, depending on genotype. Regardless of genotype, the cost-effectiveness of interferon alfa and ribavirin for patients with moderate hepatitis was lower than $50 000 per QALY vs the next best strategy. With genotype 1, pegylated interferon alfa (vs interferon alfa) and ribavirin therapy provided an additional 1.6 quality-adjusted life-months for $40 000 per QALY. Because treatment is more effective with non-1 genotypes, pegylated interferon (vs interferon alfa) and ribavirin provided only 3 additional quality-adjusted life-months for $105 300 per QALY. For patients who were intolerant of ribavirin, monotherapy with pegylated interferon was always the most cost-effective option.
Combination therapy for moderate hepatitis in coinfected patients will increase quality-adjusted life expectancy and have a cost-effectiveness ratio comparable to that of other well-accepted clinical interventions.
Archives of Internal Medicine 12/2002; 162(22):2545-56. DOI:10.1001/archinte.162.22.2545 · 17.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Catheter-related phlebitis is a frequent problem in the clinical setting. Risk factors for catheter-related phlebitis were assessed at a single tertiary-care institution where no routine change policy for peripheral intravenous catheters is in place.
In a nonrandomized, observational trial, peripheral intravenous Teflon catheters were inserted in patients with a diagnosis of leukemia, lymphoma, solid tumor, acquired immunodeficiency syndrome, other serious infection, or autoimmune disorder. Underlying disease, age, white blood cell count at the time of insertion, physician placing the catheter, catheter bore, duration of cannulation, reason for removal of the catheter, and visual inspection of the insertion site were recorded.
Four hundred twelve catheters were inserted in 175 patients. The number of catheterizations per episode varied between 1 and 7. Three hundred sixty-four (88.3%) catheter placements were evaluable. The mean duration of cannulation was 4.2 days. The overall incidence of phlebitis was 12.9%. Catheters in leukopenic patients showed a longer duration of cannulation compared with catheters in nonleukopenic patients, but no difference regarding the phlebitis rate.
Findings in this study partly contrast with data reported in the literature. In particular, leukopenia, female gender, prolonged duration of cannulation, antibiotics, and choice of insertion site could not be shown to be risk factors.
Infection Control and Hospital Epidemiology 06/2002; 23(5):249-53. DOI:10.1086/502044 · 4.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A prospective, randomized, controlled monocentric trial was performed to evaluate the efficacy and safety of once daily ceftriaxone 2 g plus gentamicin 5 mg/kg in comparison to cefepime 2 g t.i.d. plus gentamicin 5 mg/kg q.d. in the treatment of neutropenic fever. In case of fever (oral temperature > or =38.5 degrees C on one occasion or > or =38.0 degrees C twice within 24 h) and a granulocytopenia (neutrophil count below 500 or below 1000/microl when expected to fall below 500 within 72 h), patients with hematological malignancies or solid tumors were assigned to ceftriaxone or cefepime, each with gentamicin. The primary endpoint was defined as defervescence on day 4-6 followed by at least 7 afebrile days. Secondary endpoints were overall response, defined as defervescence on day 28 and toxicity. Two hundred eleven episodes were included. Fever of unknown origin (FUO) accounted for 124 episodes (58.8%), microbiologically defined infection (MDI) for 39 (18.5%), clinically defined infection (CDI) for 25 (11.8%), and both clinically and microbiologically defined infection (CMDI) for 19 episodes (9%). On an intent-to-treat basis 207 episodes were evaluable for the primary endpoint. Ceftriaxone plus gentamicin and cefepime plus gentamicin were successful in 49.5% and 51%, respectively. Overall response was achieved on study day 28 in 92.5% and 91%, respectively. Diarrhea was more frequent with ceftriaxone/gentamicin (6.5% vs 17%), while nausea/vomiting was less (12.1% vs 5%). Once-daily ceftriaxone plus gentamicin was not inferior to cefepime t.i.d. plus gentamicin q.d. in the empirical treatment of neutropenic fever.
Annals of Hematology 02/2002; 81(1):37-43. DOI:10.1007/s00277-001-0392-9 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Systemic mycosis is among the most feared opportunistic infections in the immunocompromised host. Difficulty and delay in diagnosis and treatment often result in poor outcomes. In this communication a metastatically spreading form of subcutaneous aspergillosis developed in a patient with a history of allogeneic stem cell transplantation for relapsed Hodgkin's lymphoma. Strikingly, necrotizing cutaneous papules or ulcerating lesions were absent. Diagnosis was accomplished after excision of a clinically non-suggestive subcutaneous nodule. Despite prompt initiation of antimycotic therapy the outcome was fatal; dosage of conventional and liposomal amphotericin B was limited due to treatment-related toxicities. This case report describes a novel form of aspergillosis and underlines the need for an aggressive diagnostic approach in severely immunocompromised patients.
Bone Marrow Transplantation 12/2001; 28(9):899-901. DOI:10.1038/sj.bmt.1703250 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A prospective, randomized, controlled monocentric trial was performed to evaluate the efficacy and safety of once daily ceftriaxone 2 g plus tobramycin 5 mg/kg in comparison to cefotaxime 2 g t.i.d. plus tobramycin 5 mg/kg qd in the treatment of neutropenic fever. In cases of fever > or = 38.5 degrees C and a neutrophil count below 1000/microliter, patients with hematological malignancies were assigned to ceftriaxone or cefotaxime, each with tobramycin. The primary endpoint was defined as defervescence < 37.5 degrees C on day 4-6 followed by at least 7 afebrile days. Secondary endpoints were overall response, defined as defervescence on day 25 and toxicity. There were 160 episodes of 114 patients included. Fever of unknown origin accounted for 79 episodes (51%), microbiologically defined infection for 36 (23%), clinically defined infection for 27 (17%), and both clinically and microbiologically defined infection for 14 episodes (9%). On an intent-to-treat basis 156 episodes could be evaluated for the primary endpoint. Ceftriaxone plus tobramycin and cefotaxime plus tobramycin resulted in a primary response in 46.9% and 45.3%, respectively. Overall response was achieved on study day 25 in 87.7% and 80%, respectively. No significant difference in toxicity was observed. Once-daily ceftriaxone plus tobramycin was not inferior to cefotaxime t.i.d. plus tobramycin qd in the empirical treatment of neutropenic fever.
Annals of Hematology 02/2001; 80(2):103-8. DOI:10.1007/s002770000247 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Risk factors for the HIV-associated lipodystrophy syndrome (HALS) were studied in a single-centre, cross-sectional study. -
278 consecutive HIV-infected outpatients at a German tertiary care centre were enrolled. Changes in body shape were quantified using linear analogue scales. Cumulative treatment duration for each antiretroviral drug, CD4 cells, viral load and age were investigated as potential risk factors for a clinical diagnosis of lipodystrophy syndrome by logistic regression.
HALS was diagnosed in 88 patients. The risk of HALS increased significantly with longer protease inhibitor treatment (relative risk 1.61 (95% confidence interval, 1. 24 to 2.09, per year); older age and a history of low CD4 cell counts were cofactors in this multivariate model, but nucleoside analogues did not contribute significantly. Neither pattern nor severity of disease were predicted by these risk factors. Treatment durations and other risk factors were highly correlated with each other.
These findings support a pathogenetic role for protease inhibitor toxicity, advanced HIV disease, and ageing. No evidence for an additional effect of nucleoside analogues was found. The high correlation of potential risk factors indicates that this and other available studies may be too small to detect multiple risk factors without major confounding.
European journal of medical research 11/2000; 5(10):443-8. · 1.50 Impact Factor