Antifungal Therapy in Neutropenic Oncohemopatic Patients. A Single Centre Retrospective Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5334-5334
Author(s):  
Alessandro Bonini ◽  
Alessia Tieghi ◽  
Simona Bulgarelli ◽  
Luigi Gugliotta
Keyword(s):  
High Risk ◽  
Adverse Events ◽  
Renal Insufficiency ◽  
Acute Leukemia ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Antifungal Therapy ◽  
Secondary Prophylaxis ◽  
Antifungal Treatment ◽  
Empiric Treatment

Abstract Infections are the most frequent complication during chemotherapy-induced neutropenia and fungal infections are a cause of morbility and mortality. We have retrospectively analysed our patients who received an antifungal treatment for a possible, probable or proven fungal infection. Between April 1998 and July 2005 we analysed 750 consecutive phases of treatment for 309 patients admitted at our Institution. The treatment phases were for: acute leukemia 253, lymphoma 168, multiple myeloma 215, chronic leukemia 19, severe aplastic anemia 12, solid tumors (breast, renal, testis cancer) 44, multiple sclerosis 5, others 34. Among them 474 (63.2%) were at high risk for infections (the risk was considered high for lenght of neutropenia, diagnosis of acute leukemia, allogeneic BMT). There were 31 allo-BMT and 145 autologous BMT. The antifungal therapy was for a first short period (until mid-1999) an empirical treatment (when fever persisted more than 4 days despite antibiotic therapy during neutropenia); after, only when another sign (clinical or radiological or microbiological) of fungal infection was present, the patients received an antifungal treatment. We treated also a small cohort of patients with a secondary prophylactic regimen (they were patients who developed a fungal infection during a previous treatment). Seventy-four patients received an antifungal treatment (10% of all phases and 15.6% of high-risk phases). The infection was possible (empiric treatment) in 4 cases, probable (presumptive therapy) in 37 cases, proven in 16 cases; 17 cases of secondary prophylaxis. The first administered drug was Amphotericin B deoxycholate (AMB) in 31/74 cases (41.9%), Abelcet (ABCT) in 6/74 (8%), Liposomal Amphotericin B (LAMB) in 18/74 cases (24.4%), Voriconazole (VCZ) in 3/74 cases (4%) and Caspofungin (Caspo) in 16/74 cases (21.7%). The schedule of treatment was: AMB 0.7–1 mg/Kg in 6 hours, ABCT 5 mg/Kg in 3 hours, LAMB 3 mg/Kg in 1 hour, VCZ 6 mg/Kg bid iv in 2 hours for 3 days then 4 mg/Kg bid orally, Caspo 70 mg iv on the first day and then 50 mg in 1 hour. For the empiric treatment the first drug was AMB 3 and Caspo 1; for presumptive therapy AMB 18, ABCT 4, LAMB 4, VCZ 1 and Caspo 10. For proven infections AMB 8, ABCT 1, LAMB 5, VCZ 1, Caspo 1; for secondary prophylaxis AMB 2, ABCT 1, LAMB 9, VCZ 1 and Caspo 4. The isolated fungi were Candida albicans 4, Aspergillus spp 4, Scedosporium 2, Fusarium solani 1, others (only histological isolation) 5. The days of treatment were 7.64 for AMB, 6.88 for ABCT, 14.22 for l-AMB, 14.1 for Caspo and 30 for VCZ. Adverse events with AMB and ABCT were similar: mild to moderate renal insufficiency (50%), fever (50%), ipokalemia (75%), chills (30%); with VCZ visual disturbances (80%) and mild hepatic insufficiency (20%); with LAMB mild renal insufficiency (10%) and low back pain (5%); no adverse events with Caspo were noted. AMB was discontinued 9/31 times (29%), ABCT 1/6 (17%) for adverse events. Our conclusions are that AMB and ABCT are problematic drugs for their poor tolerability, they need an important premedication, a hyperhydration regimen and a long-time administration; moreover for a great cohort of patients we have had to discontinue the drug. The other drugs seems to be better tolerated; no organ failures were seen and the treatment duration was longer for Caspo and LAMB. Even if the cost of these two drugs is major than others the lack of adverse events and the new mechanism of action of Caspo make these drugs probably better than ABCT, AMB and VCZ.

scholarly journals Successful treatment of gastrointestinal mucormycosis in an adult with acute leukemia: case report and literature review

2017 ◽  
Vol 24 (1) ◽  
pp. 61 ◽  
Author(s):  
A. Alghamdi ◽  
A. Lutynski ◽  
M. Minden ◽  
C. Rotstein
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Acute Leukemia ◽  
Fungal Infection ◽  
Antifungal Therapy ◽  
Successful Treatment ◽  
Invasive Fungal Infection ◽  
Hematologic Malignancies ◽  
Considerable Morbidity ◽  
Delays In Diagnosis

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.

Empiric Antifungal Therapy with Amphotericin B in the Era of Fluconazole Prophylaxis: a Cohort Study in Adults with Acute Myeloid Leukemia Treated within An Institutional Antifungal Policy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1390-1390
Author(s):  
Anita Adams ◽  
Tamana Hafid ◽  
Kari Kolm ◽  
Jolanta Jeziorowska ◽  
Deborah C Marcellus ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Induction Chemotherapy ◽  
Antifungal Therapy ◽  
Empiric Therapy ◽  
Best Supportive Care ◽  
Antifungal Prophylaxis ◽  
Second Line ◽  
Fluconazole Prophylaxis

Abstract Abstract 1390 Poster Board I-412 Purpose: To determine whether fluconazole prophylaxis was effective in decreasing the need for parenteral empiric antifungal therapy in patients with acute myeloid leukemia (AML) and persistent febrile neutropenia or suspected fungal infection at our center. Background: Prophylaxis with fluconazole in patients with severe chemotherapy-related neutropenia has been found to be beneficial in decreasing the need for parenteral antifungal therapy, and preventing superficial and invasive fungal infections and fungal infection-related mortality (Bow et al., Cancer 2002;94:3230-3246). Methods: The records of all patients at our hospital who presented with AML from January 1999 to July 2009 were reviewed retrospectively. As of September 2005 we adopted an institutional antifungal policy consisting of routine antifungal prophylaxis with fluconazole followed by amphotericin B as the first line parenteral agent in the event of persistent fever despite broad spectrum antibiotics or suspected fungal infection. The policy included criteria for switching from amphotericin B to a second line agent (caspofungin) for continued empiric therapy or another agent depending on clinical or laboratory data or suspicion of a particular pathogen. Explicit criteria were also developed for switching to a second line agent including baseline renal function or change in renal function while receiving amphotericin B or other adverse effects such as significant infusion reactions or electrolyte disturbances. Fluconazole was given at a dose of 400 mg daily starting with induction chemotherapy and continued until blood count recovery or switch to parenteral antifungal agent. Results: We identified a total of 170 patients with a median age of 61 years (range 18-89 years), 53 % were female and the median follow-up time was 187 days (range 2-2549 days). Baseline cytogenetics grouped patients into poor risk (40%), standard risk (39%) and favorable risk (10%) categories, with 11% unknown or inconclusive. Two-thirds of patients had de-novo AML. Twenty-four percent of patients did not receive induction chemotherapy and were treated with best supportive care, leaving 130 patients who received induction chemotherapy. Overall median survival for chemotherapy treated patients was 409 days, compared with 44 days for patients treated with best supportive care. The majority of patients (77%) who received chemotherapy were treated with standard induction consisting of 3 days of an anthracycline and 7-10 days of continuous infusion cytarabine. Of the patients treated with induction chemotherapy, 65% received prophylaxis with fluconazole and 32% did not, the remainder received prophylaxis with other antifungal agents. The use of prophylactic fluconazole coincided with implementation of our antifungal policy. Of patients who were treated with fluconazole prophylaxis, 62% required parenteral antifungal therapy and 38% did not. Of patients who did not receive fluconazole prophylaxis 56% required parenteral antifungals and 44% did not. These differences relating to receiving fluconazole prophylaxis were not statistically significantly different. For those patients requiring empiric antifungal therapy, they received a median of 18 days of fluconazole (range 3-156 days). Of the 56 patients who were treated with amphotericin B as empiric therapy, 59% were changed to another agent due to renal effects (42%), fever (27%) or other adverse effects (21%). Switching off amphotericin B occurred after a median of 7.5 days (range 0-59 days). Fifty-six percent of patients received caspofungin as the second line agent while the policy was in effect. Conclusion: Based on our retrospective analysis of the practical use of antifungal prophylaxis within our institutional antifungal policy, fluconazole prophylaxis did not decrease the need for empiric parenteral antifungal therapy. The majority of patients treated with empiric amphotericin B were switched to a second line agent, mostly due to intolerance or adverse effects. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Classical Empiric Antifungal Therapy Vs. D-Index Guided Early Therapy Using Micafungin for Persistent Febrile Neutropenia (CEDMIC trial): A Randomized Controlled Trial from Japan FN Study Group

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 816-816
Author(s):  
Shun-Ichi Kimura ◽  
Yoshinobu Kanda ◽  
Masaki Iino ◽  
Takahiro Fukuda ◽  
Emiko Sakaida ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Fungal Infection ◽  
Antifungal Therapy ◽  
Invasive Fungal Infection ◽  
Research Funding ◽  
Controlled Trial ◽  
Pharmaceutical Research ◽  
Randomized Controlled ◽  
Neutropenic Patients

Abstract Introduction: Empiric antifungal therapy (EAT) is recommended for persistent or recurrent febrile neutropenia based on an old randomized controlled trial, but such treatment is apparently overtreatment for the majority of patients. On the other hand, preemptive therapy triggered by positive blood tests for fungal antigens and/or imaging study findings was shown to increase the incidence of invasive fungal infection, and thus, a risk-based approach is important. The D-index, which is defined as the area over the neutrophil curve during neutropenia and hence reflects both the duration and depth of neutropenia (Figure 1A), enables real-time monitoring of the risk of invasive fungal infection. Previous studies showed that the cumulative D-index (c-D-index), which was calculated as cumulative D-index from the onset of neutropenia (Figure 1B), had high negative predictive values for invasive mold infection or pulmonary infection with cutoff values of 5,800 or 5,500 in high-risk neutropenic patients [J Clin Oncol 2009; 27: 3849-54. Biol Blood Marrow Transplant 2010; 16: 1355-61]. Methods: We investigated a novel approach, called D-index-guided early antifungal therapy (DET) and compared it to EAT in high-risk neutropenic patients. In the EAT group, empiric antifungal therapy was started for persistent (>=4 days) or recurrent febrile neutropenia. For patients with persistent or recurrent febrile neutropenia in the DET group, preemptive antifungal therapy was applied until c-D-index reached 5,500, but antifungal agent was initiated after c-D-index exceeded 5,500, even if there was no significant finding in serum fungal makers or imaging studies, to prevent excessive invasive fungal infection. Micafungin at 150 mg/day was administered as EAT or DET in this study. We randomized 423 patients who underwent chemotherapy or hematopoietic stem cell transplantation for hematological malignancies, in which predicted period of neutropenia exceeded 7 days, into the EAT group or the DET group, and 413 were eligible for intent-to-treat analyses (201 patients in the EAT group, 212 patients in the DET group). The prophylactic use of fluconazole or itraconazole was allowed. Primary endpoint was the development of proven/probable invasive fungal infection. Results: Backgrounds of the patients were similar between the 2 groups (Table 1). Invasive fungal infection (proven/probable/possible) was observed in 12 patients (6.0%) of the EAT group and 5 patients (2.4%) of DET group, respectively. Proven/probable invasive fungal infection was identified in 5 patients (2.5%) of the EAT group and 1 patient (0.5%) of DET group, which fulfilled the predetermined criteria of non-inferiority of the DET group. Regarding the pathogens, the EAT group included 1 case of candidemia and 4 cases of invasive pulmonary aspergillosis, and the DET group included one fusariosis. The survival rate of the EAT and DET group was 98.0% vs. 98.6% at day 42 and 96.4% vs. 96.2% at day 84, respectively. During the observation period, 31 patients died due to disease progression (n=19), infection (n=5) or other causes (n=7). Causes of infection related mortality included Pseudomonas aerginosa infection (n=2), fusariosis (n=1), toxoplasmosis (n=1) and septic shock by unknown pathogen (n=1). The frequency of micafungin use was significantly lower in the DET group than the EAT group (32.5% vs. 60.2%, P<0.001). Similar results were obtained in per-protocol set analyses. Conclusions: DET successfully reduced the use of antifungal agents without increasing invasive fungal infection or mortality compared to EAT. This randomized controlled study revealed the feasibility of DET in high-risk neutropenic patients. Disclosures Kimura: Astellas: Honoraria; Pfizer: Honoraria; Sumitomo Dainippon Pharma: Honoraria; MSD: Other: Investigator in the institute; Nippon Kayaku: Honoraria; Celgene: Honoraria; Kyowa Hakko Kirin: Honoraria; Takeda: Honoraria. Kanda:Chugai: Consultancy, Honoraria, Research Funding; Shionogi: Consultancy, Honoraria, Research Funding; Nippon-Shinyaku: Research Funding; Ono: Consultancy, Honoraria, Research Funding; MSD: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; CSL Behring: Research Funding; Kyowa-Hakko Kirin: Consultancy, Honoraria, Research Funding; Asahi-Kasei: Research Funding; Tanabe-Mitsubishi: Research Funding; Novartis: Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Otsuka: Research Funding; Dainippon-Sumitomo: Consultancy, Honoraria, Research Funding; Sanofi: Research Funding; Taisho-Toyama: Research Funding; Taiho: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Mochida: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Takara-bio: Consultancy, Honoraria. Fujiwara:Shire: Consultancy; Pfizer: Consultancy; Chugai: Consultancy; Kirin: Consultancy; Kyowa-Hakko: Consultancy; Astellas: Consultancy. Suzumiya:Celltrion: Research Funding; Taiho: Research Funding, Speakers Bureau; SymBio: Research Funding; Toyama Chemical: Research Funding; Takeda: Research Funding, Speakers Bureau; Eisai: Research Funding, Speakers Bureau; Chugai-Roche: Research Funding, Speakers Bureau; Kyowa Hakko Kirin: Research Funding, Speakers Bureau; Zenyaku Kogyo: Consultancy; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Pfizer: Research Funding; Sumitomo Dainioppon: Research Funding, Speakers Bureau; Astellas: Research Funding, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Nippon Shinyaku: Speakers Bureau; Ono: Speakers Bureau; Ohtsuka: Speakers Bureau; Shire Japan: Speakers Bureau. Takamatsu:Taisho Toyama Pharmaceutical: Research Funding; TAIHO Pharmaceutical: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding; Ono Pharmaceutical: Research Funding; Astellas Pharma: Research Funding; Kyowa Hakko Kirin: Research Funding; Chugai Pharma: Research Funding; Takeda Pharmaceutical: Research Funding; Celgene: Honoraria. Tamura:Astellas Phrma: Research Funding; Eisai: Speakers Bureau; Kyowa Hakko Kirin: Speakers Bureau; Ono Pharmaceutical: Speakers Bureau.

scholarly journals The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China

2021 ◽  
Vol 8 ◽  
Author(s):  
Ting Zhao ◽  
Xiao-lei Xu ◽  
Yan-qiu Lu ◽  
Min Liu ◽  
Jing Yuan ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Adverse Events ◽  
Antifungal Therapy ◽  
Cryptococcal Meningitis ◽  
Antifungal Treatment ◽  
Optimal Timing ◽  
Probability Of Survival ◽  
Intention To Treat ◽  
Art Initiation ◽  
Therapy Initiation

Background: The optimal timing for initiation of antiretroviral therapy (ART) in HIV-positive patients with cryptococcal meningitis (CM) has not, as yet, been compellingly elucidated, as research data concerning mortality risk and the occurrence of immune reconstitution inflammatory syndrome (IRIS) in this population remains inconsistent and controversial.Method: The present multicenter randomized clinical trial was conducted in China in patients who presented with confirmed HIV/CM, and who were ART-naïve. Subjects were randomized and stratified into either an early-ART group (ART initiated 2–5 weeks after initiation of antifungal therapy), or a deferred-ART group (ART initiated 5 weeks after initiation of antifungal therapy). Intention-to-treat, and per-protocol analyses of data for these groups were conducted for this study.Result: The probability of survival was found to not be statistically different between patients who started ART between 2–5 weeks of CM therapy initiation (14/47, 29.8%) vs. those initiating ART until 5 weeks after CM therapy initiation (10/55, 18.2%) (p = 0.144). However, initiating ART within 4 weeks after the diagnosis and antifungal treatment of CM resulted in a higher mortality compared with deferring ART initiation until 6 weeks (p = 0.042). The incidence of IRIS did not differ significantly between the early-ART group and the deferred-ART group (6.4 and 7.3%, respectively; p = 0.872). The percentage of patients with severe (grade 3 or 4) adverse events was high in both treatment arms (55.3% in the early-ART group and 41.8% in the deferred-ART group; p=0.183), and there were significantly more grade 4 adverse events in the early-ART group (20 vs. 13; p = 0.042).Conclusion: Although ART initiation from 2 to 5 weeks after initiation of antifungal therapy was not significantly associated with high cumulative mortality or IRIS event rates in HIV/CM patients compared with ART initiation 5 weeks after initiation of antifungal therapy, we found that initiating ART within 4 weeks after CM antifungal treatment resulted in a higher mortality compared with deferring ART initiation until 6 weeks. In addition, we observed that there were significantly more grade 4 adverse events in the early-ART group. Our results support the deferred initiation of ART in HIV-associated CM.Clinical Trials Registration:www.ClinicalTrials.gov, identifier: ChiCTR1900021195.

Safety and Efficacy of Caspofungin as Preventive and Empirical Antifungal Treatment of Neutropenic Allografted Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5024-5024
Author(s):  
Patrice Chevallier ◽  
Pierre Bordigoni ◽  
Thierry Lamy ◽  
Philippe Moreau ◽  
Jean-Luc Harousseau ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Therapy ◽  
Antibacterial Therapy ◽  
Conditioning Regimen ◽  
Antifungal Treatment ◽  
High Dose ◽  
Myeloablative Conditioning ◽  
Who Grade ◽  
Persistent Fever ◽  
Neutropenic Patients

Abstract Antifungal therapy is appropriate in neutropenic patients who have unexplained persistent fever, despite receipt of few days of antibacterial therapy. Conventional or liposomal amphotericin B are the preferred agents in this situation for allografted patients but toxicity or interaction with other drugs could limit their prescription. Caspofungin, the first inhibitor of fungal cell wall glucan synthesis, is the only echinocandin approved by the FDA for treatment of candidiasis. In case of suspected or documented aspergillosis infection, caspofungin is generally reserved to patients who failed to respond to amphotericin B or voriconazole. Recently, Walsh et al (ICAAC 2003) demonstrated in a randomised trial that caspofungin was comparable to liposomal amphotericine B in overall success as empirical antifungal therapy of persistently febrile neutropenic patients and was better tolerated. Here, we report our experience of caspofungin as preventive and empirical anti-fungal treatment, between November 2002 and May 2003, in 19 allografted patients with neutropenia (< 500/mm3 neutrophils) ± persistent fever despite at least 4 days of appropriate antibacterial therapy (n=12). There were 15 adult and 4 children, 11 male and 8 female. Median age was 33 years (range: 3–57). There were 6 ALL, 5 AML, 1 Myelodysplasia, 1 CML, 1 Hodgkin disease, 1 NHL, 1 myeloma, 1 aplastic anemia, 1 carcinoma and 1 Ewing sarcoma. A myeloablative conditioning regimen was used in 14 patients consisting of total body irradiation (TBI) plus high-dose chemotherapy in 9 patients and busulfan plus cyclophosphamide in 5 patients. A non myeloablative conditioning regimen was used in 5 patients. For graft-versus-host disease prophylaxis, the regimen was cyclosporin plus methotrexate in 13 patients or ATG in 6 patients. Nine patients received a bone marrow graft, 9 received granulocyte-colony-stimulating factor (G-CSF) mobilized peripheral blood stem-cells and 1 received an unrelated cord blood transplant. Twelve/19 patients have received prophylaxis with fluconazole from day 0 of the graft. Patients received caspofungin at an initial dose of 70 mg then 50 mg per day. Caspofungin was initiated within a median of 10 days after allograft (range: 0–174) including 7 patients receiving preventive caspofungin treatment at the date of aplasia. The mean duration of caspofungin therapy was 16 days (range: 3–72). Caspofungin was well tolerated and not stopped because of toxicity: WHO grade 1 and 2 hepatotoxicity occurred in 5 patients including 3 with previous hepatic abnormalities, WHO grade 1 and 2 nephrotoxicity occurred in 6 patients. No infusion reaction was observed. Only one patient developed a probable invasive bronchopulmonary aspergillosis on day 30 while receiving caspofungin. Seventeen/19 (89%) patients remain alive at least 7 days after the end of caspofungin administration without documented or suspected fungal, bacterial, or viral infection. Resolution of fever occurred in 11/12 febrile neutropenic patients in a median of 2 days (range:2–13) after starting caspofungin. We conclude that caspofungin is safe and effective as preventive and empirical antifungal treatment of neutropenic allografted patients.

Voriconazole Replacing Liposomal Amphotericin B as First-Line Therapy in Suspected or Proven Fungal Infection in Acute Leukemia Patients: A Retrospective Audit of Clinical and Financial Outcomes in a UK District Hospital.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5559-5559
Author(s):  
Jindrinska Hybnerova ◽  
Amit Bahn ◽  
Christopher Pocock
Keyword(s):  
Acute Leukemia ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Liposomal Amphotericin B ◽  
First Line ◽  
Financial Outcomes ◽  
First Line Therapy ◽  
Line Therapy ◽  
Retrospective Audit

Abstract Background: In most centres in the United Kingdom, systemic antifungal therapy (AFT) is used as third-line therapy for fever complicating profound, prolonged neutropenia (PPN) during the treatment of acute leukemia. Voriconazole has been recommended as first-line AFT at the Kent and Canterbury Hospital (KCH) since October 2002; liposomal amphotericin B was the previous treatment of choice. The aim of the audit was to identify numbers of episodes of PPN and the numbers of suspected fungal infections in a 2-year period following the policy change. Subsequently the clinical and financial outcomes were examined. In addition, the impact on cost of AFT following centralisation of leukemia treatment from two district hospitals onto one site was examined. Methods: A retrospective audit was conducted on data from hematology inpatients undergoing remission induction or consolidation therapy for acute leukemia at KCH between January 2003 and December 2004. The costs of voriconazole and liposomal amphotericin B treatment from 2002 to 2004, and 8 months prior and post centralisation of inpatient care (April 2004, which increased the population from 400,000 to 600,000), were examined. Results: 84 episodes of PPN were identified in 41 patients undergoing treatment for acute leukemia; mostly acute myeloid leukemia (AML). Itraconazole prophylaxis from d1 of therapy and GCSF from d+5 was used in the majority of cases. 18 cases of suspected or radiologically proven fungal infection were identified. High-resolution computed tomography of the chest was performed in 10 cases and suspicious lesions identified in three. Voriconazole was used as first-line therapy in 17/18 cases. In 7 cases, treatment was switched to liposomal amphotericin B. Reasons for switching were rising C-reactive protein (1 patient), persistent fever (2 patients), radiological progression (1 patient) and side effects (3 patients). Of the 3 patients with radiological evidence of fungal infection, two had a complete resolution (1 voriconazole, 1 voriconazole/liposomal amphotericin B) and 1 patient died of refractory leukemia. There was a fall in total antifungal spend from £263K in 2002/3 to £229K in 2003 and a further 68% fall to £73K in 2004. We suspect this was due to increasing adherence to the new antifungal protocol and to improved practices following centralisation: in the 8 months pre-centralisation the antifungal spend across all hospitals was £102K falling by 74% to £26K in the 8 months on the single site. Conclusion: Since introducing voriconazole as first-line AFT, centralising inpatient services, and adopting common policies for antimicrobial prophylaxis, there has been considerable financial benefit with no increase in morbidity and/or mortality.

Monitoring of 1,3-Beta-D-Glucan (BGL) Antigenemia in Neutropenic Patients with Acute Leukemia at High Risk for Invasive Fungal Infections (IFI).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2924-2924
Author(s):  
Laurence Senn ◽  
James O. Robinson ◽  
Sabine Schmidt ◽  
Marlies Knaup ◽  
Nobuo Asahi ◽  
...  
Keyword(s):  
High Risk ◽  
Early Diagnosis ◽  
Acute Leukemia ◽  
Likelihood Ratio ◽  
Median Time ◽  
Antifungal Therapy ◽  
Diagnostic Performance ◽  
Fever Onset ◽  
Neutropenic Patients ◽  
Febrile Episodes

Abstract Invasive candidiasis (IC) and aspergillosis (IA), the most frequent IFI in leukemic patients, are associated with high morbidity and mortality. As early diagnosis of IFI is difficult, empirical antifungal therapy is recommended in persistently febrile neutropenic patients. This standard of care results in a broad use of antifungals. New non-invasive diagnostic tests such as circulating BGL, a fungal cell wall component, are thus needed to optimize management of patients with IFI. The objective of the current study was to evaluate the utility of monitoring BGL antigenemia in neutropenic patients at high risk for IFI. We conducted a prospective study of 189 episodes of neutropenia (median duration 22 days, range 7–113) following induction (n=107) or consolidation chemotherapy (n=82) in 99 consecutive patients with acute leukemia (85 AML, 14 ALL). Blood was collected 2× weekly before onset of fever and daily thereafter until resolution of fever. BGL was measured by colorimetric assay (Wako, Japan). Two cut-off values (5 or 11 pg/ml) were studied. A positive result was defined by 2 consecutive samples with BGL higher than the cut-off value. A median of 2 (0–4) febrile episodes occurred per neutropenic episode. Among 320 febrile episodes, 31 IFI were diagnosed according to EORTC-MSG criteria: 17 IC (4 proven, 13 probable) and 14 IA (5 proven, 9 probable). A median of 15 samples (4–47) per episode of neutropenia were analyzed over a median period of 34 days (19–121). The diagnostic performance of BGL was evaluated in patients with proven or probable IFI compared with febrile patients without IFI (Table). In patients with IC, the median time between onset of fever as first sign of IFI and BGL positivity (>= 5) was 0 (−3 to 17 days) as compared with 16 (0 to 51 days) until diagnosis of infection using conventional microbiological and imaging techniques (p=0.03). In IA patients, it was 3 (−9 to 14 days) vs. 7 (1 to 21 days) (p=0.07). In IC and IA, median peak BGL (21 [6–111] and 15 [7–51] pg/ml) occurred on day 13 (1 to 41) and on day 7 (3 to 20) after fever onset, respectively. Median time to initiation of antifungal therapy after fever onset was similar in IC (2.5, range: 1 to 10 days) and IA (5, range: 0 to 10 days). BGL antigenemia decreased or cleared in patients responding to therapy (n=19) and continued to increase (peak 111 and 66 pg/ml) in 2 cases of IC, in whom therapy failed. BGL was negative (< 5 pg/ml) in 100/102 episodes of bacteremia. In conclusion, monitoring of 1,3-beta-D-glucan antigenemia provides a new tool for early diagnosis and follow-up of IFI in neutropenic patients with acute leukemia. Diagnostic Performance of BGL BGL Cut-off (pg/ml) 2 × 5 2 × 5 2 × 5 2 × 11 2 × 11 2 × 11 Type of proven/probable IFI IC IA All IFI IC IA All IFI Sensitivity % 65 93 76 35 43 38 Specificity % 89 89 89 99 99 99 PPV % 48 52 65 86 86 92 NPV % 94 99 93 91 93 86 Positive Likelihood Ratio 5.9 8.5 6.9 35 43 38 Negative Likelihood Ratio 0.4 0.1 0.3 0.7 0.6 0.6

Empirical Antifungal Therapy for Patients with Neutropenia and Persitent Fever - Systematic Review and Meta-Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4961-4961
Author(s):  
Elad Goldberg ◽  
Anat Gafter-Gvili ◽  
Mical Paul ◽  
Eyal Robenshtok ◽  
Liat Vidal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Amphotericin B ◽  
Antifungal Therapy ◽  
Fungal Infections ◽  
Meta Analysis ◽  
Persistent Fever ◽  
All Cause Mortality ◽  
Empirical Antifungal Therapy ◽  
Neutropenic Patients

Abstract Background: Opportunistic invasive fungal infections (IFIs) are a major concern in the management of immunocompromised patients with hematological malignancies. The practice of administering antifungal therapy to neutropenic patients with persistent fever has become a standard care. Conflicting data exists concerning the efficacy of empirical antifungal therapy. Objectives: This study aims to evaluate if empirical antifungal therapy reduces mortality and prevents invasive fungal infections (IFI). Methods: Systematic review and meta-analysis including randomized controlled trials (RCTs) comparing empirical antifungal treatment with placebo or no intervention (control), or another regimen, in neutropenic patients with persistent fever. The Cochrane Library, MEDLINE, conference proceedings and references were searched until 2007. Outcomes assessed were: All-cause mortality, documented IFI, and adverse events. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Results: Our search yielded 26 trials, 6 of which compared polyenes or azoles to control, and 20 compared between different regimens of polyenes, azoles or glucan synthesis inhibitors. Compared to control, there was no difference in all-cause mortality (RR 0.98; 95% CI 0.58–1.66, 5 trials, Fig.1). The risk for developing documented IFI was lower (RR 0.23; 95% CI 0.08–0.65, 4 trials, 4 events in the treatment group versus 18 in the control). When azoles (fluconazole, ketoconazole, itraconazole, voriconazole) were compared to polyenes (amphotericin B in 8 trials, liposomal ampho B in 1 trial) there was a trend in favor of azoles for decreased all-cause mortality (RR 0.89; 95% CI 0.73–1.09, 9 trials) and for decreased documented IFI (RR 0.70; 95% CI 0.47–1.04, 8 trials). Adverse events of any kind were less frequent in the azole group (RR 0.40; 95% CI 0.34–0.66, 5 trials), as were those which required discontinuation (RR 0.48; 95% CI 0.38–0.62, 7 trials). Conclusions: Our review demonstrates that empirical antifungal therapy does not reduce mortality. Although it reduces IFIs, data are based on a small number of trials and events. The use of amphotericin B as empirical antifungal therapy seems unwarranted since it appears to be less effective than azoles, with no mortality benefit and an increased rate of side effects. Future trials should pursue a pre-emptive approach using improved diagnostic tools (such as galactomannan testing, high resolution CT), to identify the patients for whom antifungal treatment is warranted. Figure Figure

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