RESUMO
Although rare in the U.S invasive Fusariosis (IF) is increasingly being recognized as a cause of severe invasive fungal disease in patients with neutropenia in the setting of hematologic malignancy and hematopoietic stem cell transplants (HSCT). IF in these patients is associated with high mortality, moreover there are no guidelines on effective therapy, thus early diagnosis and involvement of an expert with experience in treating Fusariosis are imperative. We present a case of IF in a patient with profound prolonged neutropenia in the setting of chemotherapy for relapsed, refractory acute myeloid leukemia. A 33-year-old woman with relapsed acute myeloid leukemia (AML) was hospitalized for re-induction chemotherapy. Five days post cycle 1 she became neutropenic. She was treated with prophylactic antimicrobials that included acyclovir, levofloxacin, and Posaconazole. On day sixty she began to run a high-grade fever. The physical exam was remarkable for a temperature of 102 degrees Fahrenheit and a heart rate of 116 beats per minute. Complete blood count was remarkable for 130 WBC/ml, Hb 6.5 g/dl, hematocrit (HCT) 18.7%, 13000 platelets/ml, absolute neutrophils counts (ANC) of 0. Her CT chest showed new bilateral lung nodules. Antibiotics were changed to cefepime, vancomycin, and metronidazole on day sixty-two without response. On day sixty-five meropenem was started and cefepime stopped. On day sixty-eight posaconazole was stopped and amphotericin B was started and two days later fever became low grade. She developed hyperpigmented skin lesions with necrotic centers on extremities that were biopsied. Histopathology staining favored the presence of rare fungal hyphae. The culture of the biopsy sample grew Fusarium spp that was identified by DNA sequencing as Fusarium falciforme. Voriconazole and terbinafine were added. Her fevers resolved within the next 24 hours and she remained afebrile. Fusarium is a hyaline mold present in the environment. Infection is acquired by inoculation into the skin, intravascular devices, or inhalation. IF incidence is low in the United States. F. solani and F. oxysporum are the most predominant disease-causing species complexes. Invasive Fusariosis (IF) is a rare disease seen in patients with hematologic malignancy and hematopoietic stem cell transplants (HSCT) with profound neutropenia. Immunocompromised patients suffer disseminated disease to multiple sites as in this case, with mortality rates of between sixty to eighty percent in this patient population. Blood and skin lesions biopsy cultures are diagnostic. Blood cultures are positive in up to sixty percent of cases in about four days. Polymerase chain reaction (PCR) can identify Fusarium but species identification by PCR is difficult. Newer molecular methods are better for species identification. Histopathology can be helpful. Differential diagnoses include invasive aspergillosis (IA), mucormycosis, mycobacterial and dimorphic fungal infections. There are no guidelines for standard therapy. Amphotericin B or voriconazole are preferred. Combination therapy may be indicated. Neutrophil recovery is crucial. Adjunctive and preventive measures have roles.
RESUMO
Management of fever in prolonged, profound neutropenia remains challenging with many possible infectious and non-infectious causes. We investigated whether procalcitonin (PCT) is superior to C-reactive protein (CRP) in discriminating between different aetiologies of fever in this setting. CRP and PCT were tested daily during 93 neutropenic episodes in 66 patients. During this study period, 121 febrile episodes occurred and were classified into four categories based on clinical and microbiological findings: microbiologically documented infection (MDI); clinically documented infection (CDI); proven or probable invasive fungal disease (IFD); fever of unknown origin (FUO). Values of PCT and CRP at fever onset as well as two days later were considered for analysis of their performance in distinguishing aetiologies of fever. At fever onset, no significant difference in PCT values was observed between different aetiologies of fever, whereas median CRP values were significantly higher in case of IFD (median 98.8 mg/L vs 28.8 mg/L, p=0.027). Both PCT and CRP reached their peak at a median of 2 days after fever onset. Median PCT values on day 2 showed no significant difference between the aetiologies of fever. Median CRP values on day 2 were significantly higher in IFD (median 172 mg/L versus 78.4 mg/L, p=0.002). In MDI median CRP values rose > 100 mg/L, whereas they did not in CDI or FUO. PCT has no added value over CRP for clinical management of fever in prolonged, profound neutropenia. When performing reassessment 2 days after fever onset, CRP has better discriminatory power between aetiologies of fever.