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Biomedical subjects

O A Cornely

Publications and source records attributed to O A Cornely.

At least 19 recordsLinked to original sources
PubMed2006

Antiviral prophylaxis in patients with haematological malignancies and solid tumours: Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Oncology (DGHO).

Morbidity and mortality in patients with malignancies are increased by viral infections. These mostly are reactivations of asymptomatic latent infections. They primarily concern clinical entities associated with the reactivation of herpes viruses, such as varicella zoster virus (VZV) and cytomegalovirus (CMV). Respiratory tract infections caused by influenza, parainfluenza or respiratory syncytial virus (RSV) are less common. Since reactivation of latent infections has major clinical impact, antiviral prophylaxis is an attractive approach for patients expecting immunosuppression. The main risk factor for clinically relevant reactivation is profound disruption of cellular immune response. Duration and severity of chemotherapy induced neutropenia are of lesser importance. The risk of viral complications rises significantly in the presence of sustained suppression of T-cell function, e.g. in recipients of allogeneic stem cell transplants or of alemtuzumab (Campath-1H) antibody therapy. The objective of this guideline is to review the basis of prophylactic strategies and to provide recommendations for clinicians treating patients with haematological malignancies and solid tumors.

Antineoplastic Agents↗
PubMed2006

A prospective, randomized multicenter trial of the empirical addition of antifungal therapy for febrile neutropenic cancer patients: results of the Paul Ehrlich Society for Chemotherapy (PEG) Multicenter Trial II.

BACKGROUND: The aim of the study was to compare the efficacy of empirical antifungals in combination with broad spectrum antibiotics with that of antibiotics alone in high risk febrile neutropenic cancer patients not responding to initial antibacterial therapy. PATIENTS AND METHODS: A prospective, randomized controlled trial was conducted at 22 cancer centers in Germany. Patients with fever of unknown origin were randomized to either piperacillin (Pip) plus an aminoglycoside (AMG) (arm A) or a third generation cephalosporin (Ceph) plus AMG (arm B). Patients not responding after 4-6 days were randomized to either imipenem (Imi) plus glycopeptide (GLP) (arm C), or Imi/GLP plus amphotericin B deoxycholate (AmB) plus 5-flucytosine (5-FC) (arm D), or Imi/GLP plus fluconazole (Fluco) (arm E). A successful outcome was defined as resolution of fever. RESULTS: In arm A, 192 of 373 patients (51.5%) responded as compared to 176 of 344 patients (51.2%) in arm B. The response rates of 155 patients randomized for further empirical treatment were 55.6%, 77.8% and 62.5% in arm C, D and E, respectively. The difference between arm C and D was of borderline statistical significance (p = 0.06) after correction for multiple testing. CONCLUSION: In neutropenic cancer patients with persistent fever the combination of antibiotics with AmB/5-FC is superior to salvage antibacterial therapy alone. There is no difference in efficacy between Pip and third generation Ceph given as initial empirical therapy in combination with an AMG.

Adolescent↗
PubMed2006

Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection.

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure.

Adult↗
PubMed2005

Caspofungin treatment in severely ill, immunocompromised patients: a case-documentation study of 118 patients.

BACKGROUND: Caspofungin has shown efficacy in empirical antifungal therapy in neutropenic patients, refractory invasive Aspergillus infections and invasive candidiasis. Here we report the currently largest series of patients treated with caspofungin outside clinical trials. METHODS: Centres in Germany that were known to treat patients with invasive fungal infections were asked to fill out detailed questionnaires for all patients treated with caspofungin. No effort was made to influence the decision to use caspofungin. RESULTS: A total of 118 patients were evaluable (median age 48 years, interquartile range 38-58), out of which 41 (35%) suffered from acute leukaemia, 31 (26%) had allogeneic stem cell transplants, 16 (14%) lymphoma or myeloma, 8 (7%) autologous stem cell transplants and 22 (19%) other causes for immunosuppression. One hundred and six patients were evaluable for efficacy out of which 68 (64%) patients achieved a complete or partial remission. A total of 81 out of 115 (70%) patients were alive 30 days after the end of caspofungin therapy. Response rates were similar in proven (20/32, 63%) and probable (27/46, 59%) infections, in neutropenic patients (41/55, 75%) and in patients who were (44/70, 63%) or were not (24/36, 67%) refractory to antifungal pre-treatment. The response rate in mechanically ventilated patients was 29% (7/24). Caspofungin was well tolerated, even in 14 patients, who were concomitantly treated with ciclosporin A, no drug-related elevations of bilirubin, alanine aminotransferase or creatinine were found. CONCLUSIONS: This open case study of severely ill patients with invasive fungal infections demonstrates both excellent efficacy and very low toxicity of caspofungin.

Adult↗
PubMed2005

Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the infectious diseases working party (AGIHO) of the german society of haematology and oncology.

Patients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Bacteria and fungi predominate the first phase until engraftment. During the second phase, from engraftment to about day 100, major infectious problems are caused by fungi and cytomegalovirus. Both pathogens remain important under continued immunosuppression, however, in the late post-transplantation period infections with encapsulated bacteria may become a problem. In this review the Infectious Diseases Working Party of the DGHO gives recommendations for prophylaxis of infections under allogeneic stem cell transplantation with drugs and other measures. The aim of the group was to do this on an evidence-based-medicine rating, if possible.

Anti-Infective Agents↗
PubMed2005

Incidence and prognosis of CMV disease in HIV-infected patients before and after introduction of combination antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV-infected patients. We studied the changes in the incidence and prognosis of cytomegalovirus (CMV) disease preceding and during the first few years of HAART in a clinic cohort. PATIENTS AND METHODS: All patients with CMV disease diagnosed between 1993 and 1999 from a clinic cohort in Cologne, Germany, were included. The patients were followed until death or until December 31, 2001. The time period from 1993-1996 was classified as pre-HAART, the period from 1997-1999 as the HAART era. Survival was analyzed with a Cox-proportional hazard model. RESULTS: From a total of 1,279 HIV-infected patients, 127 patients with CMV disease were enrolled. The incidence of CMV disease declined rapidly and significantly from 7.34 cases per 100 patient years (py) in the pre-HAART era to 0.75 cases per 100 py in the HAART era. The median survival time in the pre-HAART era was 9.5 months; the median survival was not yet reached at 4 years of follow-up in the HAART era. The only risk factors influencing survival were CD4-cell count and antiretroviral therapy before and after diagnosis of CMV disease. Treatment naive patients had a better prognosis than pretreated patients and patients treated with triple combination therapy survived longer than patients with other treatment modalities. CONCLUSION: A rapid decline in the incidence of new CMV manifestations and a better prognosis of patients with CMV disease, especially if they were treatment naive and treated with triple combination therapy, were observed in the HAART era.

AIDS-Related Opportunistic Infections↗
PubMed2005

Failure of anti-infective mouth rinses and concomitant antibiotic prophylaxis to decrease oral mucosal colonization in autologous stem cell transplantation.

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.

Adult↗
PubMed2004

Long-term outcome and quality of care of patients with Staphylococcus aureus bacteremia.

To assess the long-term outcome and influence of clinical management of patients with Staphylococcus aureus bacteremia (SAB), 229 patients with blood cultures positive for Staphylococcus aureus between January 1997 and December 2000 were retrospectively identified and followed up. Risk factors, source of infection, treatment, clinical course, and outcome were recorded by chart review. For the assessment of 1-year survival, a questionnaire was sent to family doctors and government registration offices. Time of initial antibiotic therapy, duration of antibiotic treatment and performance of echocardiography were regarded as indicators of the quality of the clinical management of SAB. Among the 229 patients studied, 218 were evaluable for 1-year survival. Crude mortality after 1 year was 37.6% year. Within 30 days 43 (19.7%) patients had died, and 39 (17.9%) additional patients died thereafter. Using multivariate analysis, the following variables were associated with death: malignant disease (odds ratio [OR] 4.8; 95% confidence interval [CI], 2.6-8.9), pneumonia (OR, 3.6; 95%CI, 1.2-10.2), age >60 years (OR, 2.6; 95%CI, 1.5-4.5), and known source of infection (OR, 2.3; 95%CI, 1.3-4.1). Among 160 patients with a completely assessable treatment course 73 (46%) had received antibiotics for at least 14 days. A delay of antibiotic treatment of 1 day or more after microbiological diagnosis was observed in 28.3% of patients (i.e., 60 of 212 patients who received at least 1 dose of antibiotics). Echocardiography was performed in 101 (44.1%) cases. Overall, the findings indicate that standard guidelines for the management of SAB are followed only in part in clinical practice. In order to reduce the considerable mortality associated with SAB and to improve short- and long-term outcome, efforts should be made to increase adherence to recommendations.

Adult↗
PubMed2004

Successful treatment of chronic disseminated candidiasis with caspofungin and itraconazole in a patient with progressive acute leukemia and prolonged neutropenia.

Severe fungal infections remain a significant cause of morbidity and mortality in neutropenic patients undergoing dose-intensive chemotherapy for malignant diseases. Chronic disseminated candidiasis (CDC) is a life-threatening complication in neutropenic patients because of the lack of responsive hematopoietic precursor cells. Resolution of Candida organ lesions after hematopoietic reconstitution may take months. Here, we report the case of a 19-year-old neutropenic woman with relapsed acute myelogenous leukemia and candidiasis of liver, spleen, and kidneys. Antifungal treatment was initiated using fluconazole and caspofungin but was changed to itraconazole and caspofungin. Despite elevated C-reactive protein (CRP) levels and detectable Candida organ lesions, antileukemic therapy was restarted with interleukin 2 at the same time as antimicrobial treatment. Eight weeks after the start of interleukin therapy, CRP levels and organ lesions were decreased significantly irrespective of continuing neutropenia. This case report describes the successful treatment of CDC during neutropenia using combination antifungal therapy and suggests controlled studies to establish optimal therapeutic strategies.

Adult↗
PubMed2003

Combination therapy of disseminated Fusarium oxysporum infection with terbinafine and amphotericin B.

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.

Amphotericin B↗
PubMed2003

Antimicrobial therapy of unexplained fever in neutropenic patients--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society).

Cytostatic chemotherapy of hematological malignancies is often complicated by neutropenia, which increases the risk of infections, especially if the neutrophil count is below 500/microl. Frequently, fever is the first, and in most patients the only, sign of an infection. Unexplained fever is defined as follows: temperature of >/=38.3 degrees C or >/=38.0 degrees C for at least 1 h, or measured twice within 12 h, if the neutrophil count is <500/microl or <1000/microl with predicted decline to 500/microl. Different risk categories can be identified according to the duration of neutropenia: low risk </=5 days, intermediate risk 6-9 days, high risk >/=10 days. An empirical mono- or duotherapy with antipseudomonal and antistreptococcal agents should be initiated immediately. In the low risk patient group, oral therapy with cipro-, levo-, or ofloxacin combined with amoxicillin/clavulanic acid is permissible. For standard and high risk patients, monotherapy can be carried out with either ceftazidime, cefepime, piperacillin with tazobactam or a carbapenem. In duotherapy, a single dose of an aminoglycoside is combined with acylaminopenicillin or a cephalosporin of the third or fourth generation. The addition of glycopeptides in empirical therapy should only be considered in the presence of severe mucositis, or if a catheter-associated infection is suspected. If fever persists after 72-96 h of first-line therapy with antibiotics, the regimen should be modified (with the exception of e.g. coagulase-negative staphylococci infections, because these infections take longer to respond). Intermediate risk patients should additionally receive an aminoglycoside after monotherapy (penicillin or a cephalosporin). If a carbapenem was administered for monotherapy, this can be followed by a quinolone and/or a glycopeptide. In the high risk group, the same modifications should be made as in the intermediate risk group but with additional systemic antifungal treatment. In the presence of unexplained fever, fluconazole can be administered at first, but if this fails, amphotericin B (conventional or liposomal), itraconazole, voriconazole or caspofungin should be started. After defervescence to <38 degrees C, treatment should be continued for 7 days if the neutrophil count is <1000/microl, and for 2 days if the neutrophil count is >1000/microl.

Anti-Bacterial Agents↗
PubMed2003

Ceftriaxone in febrile neutropenia.

Standard management of febrile neutropenia requires prompt administration of empirical, broad-spectrum antibiotic therapy, since febrile neutropenia is associated with a significant risk of infectious complications and mortality. Risk-assessment models have been developed that differentiate febrile patients with neutropenia according to their risk for infectious complications and/or mortality and have prompted a change in the management of these patients. Ceftriaxone is a long-lasting, broad spectrum cephalosporin which has demonstrated efficacy in this indication in many publications. The role of ceftriaxone in febrile neutropenia will be discussed based on literature analysis and on the author's experience.

Anti-Bacterial Agents↗
PubMed2002

The first echinocandin: caspofungin.

The antifungal agent caspofungin is the first echinocandin that has been approved in the US and in Europe for treatment of invasive aspergillosis in adult patients who are refractory to or intolerant of conventional amphotericin B, its lipid-based formulations, and/or itraconazole. It is given as a 70 mg loading dose and a 50 mg daily maintainance dose as a one hour infusion. Due to low intestinal absorption an oral formulation has not been developed. Caspofungin is active against Candida spp. and Aspergillus spp. by inhibition the synthesis of beta-(1,3)-D-glucan, a cell wall component. The drug is inactive against Cryptococcus spp., Fusarium spp., Trichosporon spp., Rhizopus spp., and Pseudoallescheria spp. In invasive aspergillosis caspofungin resulted in higher response rates compared to a historic control under standard therapy. Efficacy data on persistently febrile neutropenic patients are pending. In several multicenter randomised double blind trials on candida infections caspofungin proved to be at least non-inferior to standard therapies. Reports of combination therapy or highly effective antifungal treatment (HEAT) in limited patient numbers are promising. New trials of combination therapy are warranted.

Acremonium↗
PubMed2001

A randomized monocentric trial in febrile neutropenic patients: ceftriaxone and gentamicin vs cefepime and gentamicin.

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.

Anti-Bacterial Agents↗
PubMed2001

Randomized controlled monocentric comparison of once daily ceftriaxone with tobramycin and cefotaxime three times daily with tobramycin in neutropenic fever.

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.

Adult↗
PubMed2001

Acute anterior myocardial infarction as first manifestation of acute myeloid leukemia.

A 42-year-old man was admitted with heavy retrosternal pain lasting 30 min. Electrocardiography showed typical signs of acute anterior myocardial infarction. The patient reported only attacks of coughing for a couple of days, and no serious diseases. The physical examination was normal. Laboratory tests showed a white blood cell count of 45/nl, platelet count of 58/nl, and hemoglobin of 14.4 g/dl. Blood chemistry showed elevated lactic dehydrogenase (413 U/l) but no elevation in creatine phosphokinase or glutamic-oxaloacetic transaminase. Therefore no thrombolysis was administered, but coronary angiography was performed. This showed a long-distance, subtotal thrombotic occlusion of the left anterior descending artery. After percutaneous transluminal coronary angioplasty and implantation of serial stents a normal perfusion of the artery was observed. The patient's blood and bone marrow films revealed acute myeloid leukemia FAB M2. Various conditions can cause a myocardial infarction in leukemias. We discuss the clinical management and the possible reasons for a subtotal thrombotic occlusion of the coronary artery.

Adult↗
PubMed2001

A novel type of metastatically spreading subcutaneous aspergillosis without epidermal lesions following allogeneic stem cell transplantation.

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.

Adult↗