scholarly journals Posaconazole DR Tablet Serum Concentrations in the Bone Marrow Transplant Population: Association with Prevention or Treatment of Invasive Fungal Infections

2015 ◽  
Vol 21 (2) ◽  
pp. S251-S252
Author(s):  
Nina Haste ◽  
David R. Ha ◽  
Katherine Medley ◽  
Charles James ◽  
Randy Taplitz
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Fungal Infections ◽  
Marrow Transplant ◽  
Invasive Fungal Infections ◽  
Serum Concentrations ◽  
Population Association

scholarly journals Voriconazole Monitoring in Children with Invasive Fungal Infections

2015 ◽  
Vol 20 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Lyn Tucker ◽  
Tara Higgins ◽  
Eric F. Egelund ◽  
Baiming Zou ◽  
Vini Vijayan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Pediatric Oncology ◽  
Trough Concentration ◽  
Fungal Infections ◽  
Dose Range ◽  
Marrow Transplant ◽  
Invasive Fungal Infections ◽  
Transplant Patients ◽  
Trough Concentrations

OBJECTIVES: The primary objective of this study was to determine the optimal daily dose of voriconazole required to achieve therapeutic trough concentrations in children 1 month to 18 years of age. The secondary objective was to analyze the association between voriconazole trough concentrations and clinical and microbiological outcomes, toxicity, and mortality. METHODS: This study was a retrospective chart review (October 2009 to August 2012) of pediatric oncology/bone marrow transplant patients with proven or probable invasive fungal infections treated with intravenous or oral voriconazole. Patients were excluded if they were older than 18 years of age, had no voriconazole concentrations drawn during the study period, or received voriconazole prior to the study period. RESULTS: Thirty-four patients were reviewed; 11 patients met all criteria for inclusion. There were 6 males and 5 females, with a median age of 8 years (range: 0.8–14.8) and a median weight of 27 kg (range: 9–74). Doses were adjusted to a median 6 mg/kg/dose (range: 3–8.7 mg/kg/dose) given every 8 (n = 5) to 12 (n = 6) hours; dose regimens varied greatly. All but 1 child achieved a voriconazole trough concentration above 1 mg/L; 7 children had a trough concentration above 2 mg/L. The median time to achieve a therapeutic trough concentration was 11 days (range: 6–37 days). Therapy failed for 4 of 11 patients, including 3 of the 4 youngest patients (p=0.022). Three of the 4 for whom therapy failed also had voriconazole trough concentrations less than 2 mg/L; this did not reach statistical significance. Voriconazole therapy was discontinued in 2 patients due to toxicity. CONCLUSIONS: This study confirmed that voriconazole pharmacokinetics vary greatly in pediatric oncology/bone marrow transplant patients. “Optimal” doses varied over nearly a 3-fold range. Younger patients may be at greater risk of poor outcomes and may require additional monitoring and dose adjustment.

Effect of Infusion Rate on Amphotericin B-Associated Febrile Reactions

1988 ◽  
Vol 22 (10) ◽  
pp. 769-772 ◽  
Author(s):  
John D. Cleary ◽  
Daniel Weisdorf ◽  
Courtney V. Fletcher
Keyword(s):  
Bone Marrow ◽  
Amphotericin B ◽  
Bone Marrow Transplant ◽  
Cardiac Disease ◽  
Infusion Rate ◽  
Adverse Reactions ◽  
Fungal Infections ◽  
Marrow Transplant ◽  
Transplant Recipients ◽  
Axillary Temperature

Our objective was to prospectively study febrile and chill reactions associated with two amphotericin B (AB) infusion rates, slow (2-hour) versus rapid (45 minute). Seventeen consenting bone marrow transplant recipients in whom AB was to be initiated for documented or suspected fungal infections were recruited. After standardized premedication, patients received eight daily AB infusions (0.5 mg/kg/d, concentration 0.25 mg/ml). Rate was assigned using a randomized, crossover pair design. Axillary temperature, chills, and meperidine dose required to resolve chills were monitored for each infusion. For the first pair of infusions, fever (defined as a rise of 1 °C) occurred frequently, in 12 of 17 (70.5 percent) and 13 of 17 patients (76.4 percent), with a mean rise of 1.7 °C (range 1.1–3.7) and 1.7 °C (1.1–3.5) degrees for the 45-minute and 2-hour infusions, respectively (p > 0.10). Chills were observed in 15 of 17 (88.2 percent) and 14 of 17 (82.3 percent) recipients of the 45-minute and 2-hour infusions, respectively. The time of onset (p > 0.10) and the duration of chills (p = 0.08) were similar for both infusion rates. Meperidine requirements for rapid and slow infusions were similar as well (p = 0.12). These data suggest that for patients free of preexisting renal and cardiac disease, rapid AB infusions are well tolerated and produce adverse reactions (fever and chills) similar in nature and severity to slower infusions.

Impact of Surgical Treatment on Paranasal Fungal Infections in Bone Marrow Transplant Patients

1997 ◽  
Vol 116 (6) ◽  
pp. 610-616 ◽  
Author(s):  
Cynthia A. Kennedy ◽  
George L. Adams ◽  
Joseph R Neglia ◽  
G. Scott Giebink
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Surgical Intervention ◽  
Fungal Infections ◽  
Systemic Disease ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Fungal Sinusitis ◽  
Cell Counts ◽  
Immunosuppressed Patients

Invasive fungal sinusitis can develop in immunosuppressed patients. A more complex problem is immunosuppressed patients who have undergone bone marrow transplantation. For a prolonged period, they are both neutropenic and thrombocytopenic. Survival in these patients is poor, and the role for extensive surgical intervention for sinus disease has to be weighed against the risk and the potential that this is a systemic disease. Between January 1983 and June 1993, 29 bone marrow transplant recipients with documented invasive fungal infections of the sinuses and paranasal tissues required surgical intervention. This represents 1.7% of the total 1692 bone marrow transplants performed. There were 22 allogeneic, 6 autologous, and 3 unrelated donor transplants, with two patients receiving two separate grafts. Underlying diseases included 24 hematologic malignancies and 5 other disorders, including 1 aplastic anemia and 1 solid tumor. The mortality rate from the initial fungal infection was 62%. Twenty-seven percent resolved the initial infections but subsequently died of other causes. All patients received medical management, such as amphotericin, rifampin, and colony-stimulating factors, in addition to surgical intervention. Surgical management ranged from minimally invasive procedures to extensive resections including medial maxillectomies. Sixty-one percent of the patients who died of the initial infection had undergone extensive surgical procedures versus 55% of those who resolved the infection. Recovery of neutrophil counts was required to clear the infection but did not necessarily predict a good outcome because 50% of those who died of the infection had experienced neutrophil recovery. White blood cell counts at the time of surgery were not significantly different between the two groups. Prognosis was poor when cranial and orbital involvement and/or bony erosion occurred.

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