Fatal Rhizopus Pneumonia in Allogeneic Stem Cell Transplant Patients Despite Posaconazole Prophylaxis: Two Cases and Review of the Literature

Lekakis, Lazaros J.; Lawson, Amber; Prante, Jeanette; Ribes, Julie A.; Davis, Gregory J.; Monohan, Gregory; Baraboutis, Ioannis G.; Skoutelis, Athanasios; Howard, Dianna S.

doi:10.1016/j.bbmt.2009.04.007

Cited by 47 publications

(36 citation statements)

References 32 publications

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“…77 Compliance issues, suboptimal absorption, and drug-drug interactions frequently result in low posaconazole serum levels and occasional breakthrough mucormycosis infections. 49 It is also unclear whether posaconazole use and suboptimal pharmacokinetics are driving forces behind culture-negative breakthrough mucormycosis. In view of the ever low autopsy rates, 13 the lack of cultureindependent serum-based surrogate diagnostic markers and prospective surveillance of trends in epidemiology of various opportunistic fungal infections, the answer may never be known.…”

Section: Prevention Prophylaxis and Infection Controlmentioning

confidence: 99%

“…45 It is common for hematologic malignancy patients to have multiple risk factors for malabsorption, frequently leading to undetectable serum concentrations and increased risk of breakthrough infection. 42,44,49 Indeed, one-third of patients at the M. D. Anderson Cancer Center who do not have mucositis or gut graft-versus-host disease still have suboptimal plasma concentrations of posaconazole with maximal doses, emphasizing that suboptimal pharmacokinetics cannot be predicted just on the basis of clinical patient characteristics alone (D.P.K., unpublished data, 2010). Unfortunately, an intravenous formulation of posaconazole is not currently available, and absorption of the drug is limited at 800 mg/d when administered with food in divided doses (2-4 times daily).…”

Section: Mucormycosis 1219mentioning

confidence: 99%

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How I treat mucormycosis

Kontoyiannis

Lewis

2011

Blood

320

311

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Unlike invasive aspergillosis, the prognosis and outcome of hematologic malignancy patients who develop invasive mucormycosis have not significantly improved over the past decade as a majority of patients who develop the infection still die 12 weeks after diagnosis. However, early recognition and treatment of invasive mucormycosis syndromes, as well as individualized approaches to treatment and secondary prophylaxis, could improve the odds of survival, even in the most persistently immunosuppressed patient receiving chemotherapy and/or of stem cell transplantation. Herein, we describe the subtle clinical and radiographic clues that should alert the hematologist to the possibility of mucormycosis, and aggressive and timely treatment approaches that may limit the spread of infection before it becomes fatal. Hematology patients with this opportunistic infection require integrated care across several disciplines and frequently highly individualized and complex sequence of decision-making. We also offer perspectives for the use of 2 antifungals, amphotericin B products and posaconazole, with activity against Mucorales. The availability of posaconazole in an oral formulation that can be administered safely for prolonged periods makes it an attractive agent for long-term primary and secondary prophylaxis. However, serum drug concentration monitoring may be required to minimize breakthrough infection or relapsing mucormycosis associated with inadequate blood concentrations. (Blood. 2011;118(5):1216-1224) IntroductionMucormycosis is the unifying term used to describe infections caused by fungi belonging to the order Mucorales. Zygomycosis, an alternative term used to describe these life-threatening infections, has become less accurate based on a recent taxonomic reclassification (based on molecular identification) that abolished Zygomycetes as a class. [1][2][3][4] Rhizopus, Mucor, and Rhizomucor species account for up to 75% of mucormycosis cases encountered in hematologic malignancy patients. [5][6][7] Mucorales typically cause acute, aggressive, and frequently angioinvasive infections, especially in immunosuppressed hosts with hematologic malignancy and/or stem cell transplantation (SCT). 8,9 This opportunistic, geographically broad mycosis was highlighted as a sporadic cause of death in leukemia patients in the 1950s 10 until the mid 1990s where there has been an apparent increase in the documented cases in hematology units throughout the Westernized world ( Figure 1). [4][5][6][7]11 These cases are typically considered community-acquired, as nosocomial cases are less common in modern SCT and transplant units. 12 However, the true incidence of mucormycosis is not known and probably underestimated because of difficulties in antemortem diagnosis and the low autopsy rates in contemporary patients who die in the setting of leukemia or SCT. 13 The predisposing factors for mucormycosis in patients with hematologic cancer are similar to ones encountered in other opportunistic mold infections, such as aspergillosis, includi...

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Section: Prevention Prophylaxis and Infection Controlmentioning

confidence: 99%

Section: Mucormycosis 1219mentioning

confidence: 99%

How I treat mucormycosis

Kontoyiannis

Lewis

2011

Blood

320

311

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“…22 Nevertheless, there are also emerging reports of breakthrough infections by agents of mucormycosis in patients receiving prophylactic posaconazole. [74][75][76] This means that even if a patient is on posaconazole prophylaxis, mucormycosis should be included in the differential diagnosis if signs of an invasive fungal infection are found.…”

Section: Posaconazolementioning

confidence: 99%

Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3)

et al. 2012

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“…It is not surprising that Fusarium breakthrough occurred during fluconazole and during caspofungin treatment as neither of the two drugs has in vivo or in vitro activity, whereas breakthrough during voriconazole treatment or prophylaxis requires full investigation to find out whether this was a result of inadequate drug levels or acquired resistance, as voriconazole is a highly active drug against Fusarium spp. Though there are several reports of breakthrough Zygomycosis and other fungi in patients receiving posaconazole prophylaxis [8][9][10][11][12] and two case reports of breakthrough Fusarium spp. in patients receiving voriconazole prophylaxis, [7,13] there are no previous reports of breakthrough Fusarium infection in a patient on posaconazole prophylaxis.…”

Section: Case Reportmentioning

confidence: 99%