IMPACT OF POSACONAZOLE PROPHYLAXIS ON INVASIVE FUNGAL INFECTION, ASPERGILLUS GALACTOMANNAN AND PERSISTENT FEBRILE NEUTROPENIA DURING AML INDUCTION THERAPY: A SINGLE-CENTER, REAL-LIFE EXPERIENCE
(Abstract release date: 05/21/15)
EHA Library. Sampath V. 06/12/15; 102580; PB1809
Disclosure(s): Tan Tock Seng HospitalHaematology
Venkata Sreekanth Sampath
Contributions
Contributions
Abstract
Abstract: PB1809
Type: Publication Only
Background
Posaconazole prophylaxis has been shown to prevent invasive fungal infection(IFI) in acute myeloid leukaemia (AML) patients during induction therapy. The role of serum aspergillus galactomannan(GM) in diagnosis of invasive fungal infection and the optimal management of persistent febrile neutropenia during posaconazole prophylaxis is less clear.
Aims
The aims of this study are to determine in patients having AML induction chemotherapy with posaconazole prophylaxis, the incidence of IFI, the role of GM in diagnosis and premptive antifungal treatment and the management of persistent febrile neutropenia for more than 96 hours despite broad-spectrum antibiotics.
Methods
We collected prospective data on 22 consecutive patients undergoing AML induction chemotherapy with posaconazole prophylaxis between August 2013 and November 2014. Induction chemotherapy comprised duanorubicin 45-90 mg/m2 for 3 days and cytarabine 100 mg/m2 for 7 days. Oral posaconazole was started on day 1 of chemotherapy. Patients not in complete remission received salvage reinduction chemotherapy. Serum posaconazole levels were not done. GM was performed once or twice weekly.Patients who had persistent febrile neutropenia for more than 96 hours despite broad spectrum antibiotics were investigated with computed tomography. Respiratory consult for broncho-alveolar lavage was discretionary. Empirical antifungal therapy was commenced if the patient was clinically unstable or had radiological findings of probable IFI.
Results
IFI(aspergillus flavus sinusitis) was diagnosed in 1 out of 22 patients (4.55%) during the first cycle of induction chemotherapy. Probable invasive pulmonary aspergillosis was diagnosed in one patient during salvage chemotherapy. Both infections were fatal. Both patients had radiological findings but negative serum GM levels and diarrhoea at the time of diagnosis. One patient had a single positive serum GM (GM index of 0.9) two weeks prior to the diagnosis of IFI but was deemed to be false-positive as he was afebrile and asymptomatic. Serum GM was done on 179 occasions but was positive only once (0.56%) which was deemed false-positive. Persistent febrile neutropenia for more than 96 hours despite broad spectrum antibiotics were seen in 17 patients (77.27%). Computed tomography showed radiological findings suggestive of chest infection in 9 patients (40.9%) and sinusitis in 3 patients (13.63%). Positive blood cultures were seen in 10 patients with febrile neutropenia (45.45%). 4 patients(18.19%) had antifungal treatment. BAL was performed in one patient and did not reveal any specific microbiology.
Summary
Posaconazole is effective antifungal prophylaxis in AML patients undergoing induction chemotherapy. Diarrhoea may impair posaconazole absorption and may have lead to invasive fungal infection in the two patients but posaconazole levels were not done. Therapeutic drug monitoring may be useful as IFI are uncommon with adequate levels. Serum GM is not useful in the diagnosis and initiation of preemptive antifungal therapy with posaconazole prophylaxis. Persistent febrile neutropenia should not be automatically an indication for empirical antifungal therapy in all patients. Individualised decision making is needed in this context. Assessment of serum posaconazole levels, computed tomography, broncho-alveolar lavage with BAL galactomannan and the clinical status of the patient may be the best approach to initiate antifungal therapy with posaconazole prophylaxis in persistent febrile neutropenia of unknown origin. Empirical antifungal therapy is an alternative option but may increase treatment cost and drug resistance. Invasive fungal infection in the setting of posaconazole prophylaxis is difficult to treat and often fatal.
Keyword(s): Acute myeloid leukemia, Anti-fungal prophylaxis, Febrile neutropenia, Fungal infection
Type: Publication Only
Background
Posaconazole prophylaxis has been shown to prevent invasive fungal infection(IFI) in acute myeloid leukaemia (AML) patients during induction therapy. The role of serum aspergillus galactomannan(GM) in diagnosis of invasive fungal infection and the optimal management of persistent febrile neutropenia during posaconazole prophylaxis is less clear.
Aims
The aims of this study are to determine in patients having AML induction chemotherapy with posaconazole prophylaxis, the incidence of IFI, the role of GM in diagnosis and premptive antifungal treatment and the management of persistent febrile neutropenia for more than 96 hours despite broad-spectrum antibiotics.
Methods
We collected prospective data on 22 consecutive patients undergoing AML induction chemotherapy with posaconazole prophylaxis between August 2013 and November 2014. Induction chemotherapy comprised duanorubicin 45-90 mg/m2 for 3 days and cytarabine 100 mg/m2 for 7 days. Oral posaconazole was started on day 1 of chemotherapy. Patients not in complete remission received salvage reinduction chemotherapy. Serum posaconazole levels were not done. GM was performed once or twice weekly.Patients who had persistent febrile neutropenia for more than 96 hours despite broad spectrum antibiotics were investigated with computed tomography. Respiratory consult for broncho-alveolar lavage was discretionary. Empirical antifungal therapy was commenced if the patient was clinically unstable or had radiological findings of probable IFI.
Results
IFI(aspergillus flavus sinusitis) was diagnosed in 1 out of 22 patients (4.55%) during the first cycle of induction chemotherapy. Probable invasive pulmonary aspergillosis was diagnosed in one patient during salvage chemotherapy. Both infections were fatal. Both patients had radiological findings but negative serum GM levels and diarrhoea at the time of diagnosis. One patient had a single positive serum GM (GM index of 0.9) two weeks prior to the diagnosis of IFI but was deemed to be false-positive as he was afebrile and asymptomatic. Serum GM was done on 179 occasions but was positive only once (0.56%) which was deemed false-positive. Persistent febrile neutropenia for more than 96 hours despite broad spectrum antibiotics were seen in 17 patients (77.27%). Computed tomography showed radiological findings suggestive of chest infection in 9 patients (40.9%) and sinusitis in 3 patients (13.63%). Positive blood cultures were seen in 10 patients with febrile neutropenia (45.45%). 4 patients(18.19%) had antifungal treatment. BAL was performed in one patient and did not reveal any specific microbiology.
Summary
Posaconazole is effective antifungal prophylaxis in AML patients undergoing induction chemotherapy. Diarrhoea may impair posaconazole absorption and may have lead to invasive fungal infection in the two patients but posaconazole levels were not done. Therapeutic drug monitoring may be useful as IFI are uncommon with adequate levels. Serum GM is not useful in the diagnosis and initiation of preemptive antifungal therapy with posaconazole prophylaxis. Persistent febrile neutropenia should not be automatically an indication for empirical antifungal therapy in all patients. Individualised decision making is needed in this context. Assessment of serum posaconazole levels, computed tomography, broncho-alveolar lavage with BAL galactomannan and the clinical status of the patient may be the best approach to initiate antifungal therapy with posaconazole prophylaxis in persistent febrile neutropenia of unknown origin. Empirical antifungal therapy is an alternative option but may increase treatment cost and drug resistance. Invasive fungal infection in the setting of posaconazole prophylaxis is difficult to treat and often fatal.
Keyword(s): Acute myeloid leukemia, Anti-fungal prophylaxis, Febrile neutropenia, Fungal infection
Abstract: PB1809
Type: Publication Only
Background
Posaconazole prophylaxis has been shown to prevent invasive fungal infection(IFI) in acute myeloid leukaemia (AML) patients during induction therapy. The role of serum aspergillus galactomannan(GM) in diagnosis of invasive fungal infection and the optimal management of persistent febrile neutropenia during posaconazole prophylaxis is less clear.
Aims
The aims of this study are to determine in patients having AML induction chemotherapy with posaconazole prophylaxis, the incidence of IFI, the role of GM in diagnosis and premptive antifungal treatment and the management of persistent febrile neutropenia for more than 96 hours despite broad-spectrum antibiotics.
Methods
We collected prospective data on 22 consecutive patients undergoing AML induction chemotherapy with posaconazole prophylaxis between August 2013 and November 2014. Induction chemotherapy comprised duanorubicin 45-90 mg/m2 for 3 days and cytarabine 100 mg/m2 for 7 days. Oral posaconazole was started on day 1 of chemotherapy. Patients not in complete remission received salvage reinduction chemotherapy. Serum posaconazole levels were not done. GM was performed once or twice weekly.Patients who had persistent febrile neutropenia for more than 96 hours despite broad spectrum antibiotics were investigated with computed tomography. Respiratory consult for broncho-alveolar lavage was discretionary. Empirical antifungal therapy was commenced if the patient was clinically unstable or had radiological findings of probable IFI.
Results
IFI(aspergillus flavus sinusitis) was diagnosed in 1 out of 22 patients (4.55%) during the first cycle of induction chemotherapy. Probable invasive pulmonary aspergillosis was diagnosed in one patient during salvage chemotherapy. Both infections were fatal. Both patients had radiological findings but negative serum GM levels and diarrhoea at the time of diagnosis. One patient had a single positive serum GM (GM index of 0.9) two weeks prior to the diagnosis of IFI but was deemed to be false-positive as he was afebrile and asymptomatic. Serum GM was done on 179 occasions but was positive only once (0.56%) which was deemed false-positive. Persistent febrile neutropenia for more than 96 hours despite broad spectrum antibiotics were seen in 17 patients (77.27%). Computed tomography showed radiological findings suggestive of chest infection in 9 patients (40.9%) and sinusitis in 3 patients (13.63%). Positive blood cultures were seen in 10 patients with febrile neutropenia (45.45%). 4 patients(18.19%) had antifungal treatment. BAL was performed in one patient and did not reveal any specific microbiology.
Summary
Posaconazole is effective antifungal prophylaxis in AML patients undergoing induction chemotherapy. Diarrhoea may impair posaconazole absorption and may have lead to invasive fungal infection in the two patients but posaconazole levels were not done. Therapeutic drug monitoring may be useful as IFI are uncommon with adequate levels. Serum GM is not useful in the diagnosis and initiation of preemptive antifungal therapy with posaconazole prophylaxis. Persistent febrile neutropenia should not be automatically an indication for empirical antifungal therapy in all patients. Individualised decision making is needed in this context. Assessment of serum posaconazole levels, computed tomography, broncho-alveolar lavage with BAL galactomannan and the clinical status of the patient may be the best approach to initiate antifungal therapy with posaconazole prophylaxis in persistent febrile neutropenia of unknown origin. Empirical antifungal therapy is an alternative option but may increase treatment cost and drug resistance. Invasive fungal infection in the setting of posaconazole prophylaxis is difficult to treat and often fatal.
Keyword(s): Acute myeloid leukemia, Anti-fungal prophylaxis, Febrile neutropenia, Fungal infection
Type: Publication Only
Background
Posaconazole prophylaxis has been shown to prevent invasive fungal infection(IFI) in acute myeloid leukaemia (AML) patients during induction therapy. The role of serum aspergillus galactomannan(GM) in diagnosis of invasive fungal infection and the optimal management of persistent febrile neutropenia during posaconazole prophylaxis is less clear.
Aims
The aims of this study are to determine in patients having AML induction chemotherapy with posaconazole prophylaxis, the incidence of IFI, the role of GM in diagnosis and premptive antifungal treatment and the management of persistent febrile neutropenia for more than 96 hours despite broad-spectrum antibiotics.
Methods
We collected prospective data on 22 consecutive patients undergoing AML induction chemotherapy with posaconazole prophylaxis between August 2013 and November 2014. Induction chemotherapy comprised duanorubicin 45-90 mg/m2 for 3 days and cytarabine 100 mg/m2 for 7 days. Oral posaconazole was started on day 1 of chemotherapy. Patients not in complete remission received salvage reinduction chemotherapy. Serum posaconazole levels were not done. GM was performed once or twice weekly.Patients who had persistent febrile neutropenia for more than 96 hours despite broad spectrum antibiotics were investigated with computed tomography. Respiratory consult for broncho-alveolar lavage was discretionary. Empirical antifungal therapy was commenced if the patient was clinically unstable or had radiological findings of probable IFI.
Results
IFI(aspergillus flavus sinusitis) was diagnosed in 1 out of 22 patients (4.55%) during the first cycle of induction chemotherapy. Probable invasive pulmonary aspergillosis was diagnosed in one patient during salvage chemotherapy. Both infections were fatal. Both patients had radiological findings but negative serum GM levels and diarrhoea at the time of diagnosis. One patient had a single positive serum GM (GM index of 0.9) two weeks prior to the diagnosis of IFI but was deemed to be false-positive as he was afebrile and asymptomatic. Serum GM was done on 179 occasions but was positive only once (0.56%) which was deemed false-positive. Persistent febrile neutropenia for more than 96 hours despite broad spectrum antibiotics were seen in 17 patients (77.27%). Computed tomography showed radiological findings suggestive of chest infection in 9 patients (40.9%) and sinusitis in 3 patients (13.63%). Positive blood cultures were seen in 10 patients with febrile neutropenia (45.45%). 4 patients(18.19%) had antifungal treatment. BAL was performed in one patient and did not reveal any specific microbiology.
Summary
Posaconazole is effective antifungal prophylaxis in AML patients undergoing induction chemotherapy. Diarrhoea may impair posaconazole absorption and may have lead to invasive fungal infection in the two patients but posaconazole levels were not done. Therapeutic drug monitoring may be useful as IFI are uncommon with adequate levels. Serum GM is not useful in the diagnosis and initiation of preemptive antifungal therapy with posaconazole prophylaxis. Persistent febrile neutropenia should not be automatically an indication for empirical antifungal therapy in all patients. Individualised decision making is needed in this context. Assessment of serum posaconazole levels, computed tomography, broncho-alveolar lavage with BAL galactomannan and the clinical status of the patient may be the best approach to initiate antifungal therapy with posaconazole prophylaxis in persistent febrile neutropenia of unknown origin. Empirical antifungal therapy is an alternative option but may increase treatment cost and drug resistance. Invasive fungal infection in the setting of posaconazole prophylaxis is difficult to treat and often fatal.
Keyword(s): Acute myeloid leukemia, Anti-fungal prophylaxis, Febrile neutropenia, Fungal infection
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