A disseminated filamentous fungal infection that broke through echinocandin antifungal treatment
Case history 1
34-year-old female, 15 days after allogeneic hematopoietic stem cell transplant for acute
myelogenous leukemia. Her white blood cell count had been <100/μL for about 20 days andwas expected to begin recovering soon.
She had been treated with carbapenems, glycopeptides, and candin antifungals for over tendays for a persistent fever, and had received acyclovir as prophylaxis. Painful skin rashes
appeared on the right ankle, knees, left thigh, and right armpit 4.5 days ago. (See photo 1, left)
Photo 1: Rash on left thighCT 1: Disseminated lesionsof left lung

Vital signs and laboratory findings 1
Temperature 39.6C, blood pressure 104/58, heart rate 118 bpm,
respiratory rate 16, and O2 saturation 98%.
Slight discomfort in right costal region. Mild redness andtenderness around anus (signs of improvement observed).
No other significant symptoms or physical abnormalities observed.
WBC 100/μL, Hgb 11.8 g/dL, Plt 39,000/μL, T-Bil 0.7 g/dL,
GOT 17 IU/L, GPT 57 IU/L, LDH 86 IU/L, ALP 406 IU/L
Beta-d-glucan 10.5pg/ml <20, Aspergillus GM antigen negative
Blood culture, skin biopsy, and whole body CT scan performed.
Disseminated lesion in lung field (CT 1), biopsy revealed
filamentous fungus (Photo 2)
Tissue culture identified Fusarium oxysporum, blood culture wasnegative

Clinical course 2
Skin rash disappeared after antifungal drug was changed tovoriconazole. Eighteen days post-transplant, blood cell countstarted recovering and fever subsided.
Prednisolone 1mg/kg started for graft versus host disease(GvHD).
Fever returned and skin rash appeared on extremities 29 days
post-transplant.
Vital signs and laboratory findings 2Tapping pain in right costal region, left abdomen and backWBC 8300/μL, T-Bil 0.3 g/dL, GOT 28 IU/L, GPT 87 IU/L, LDH
153 IU/L, ALP 518 IU/L ,Beta-d-glucan 85.1 pg/ml, Aspergillus
GM antigen negative
Skin biopsy detected same filamentous fungi in an initial test,
all cultures negative
Fusarium susceptibility profiles: Amphotericin B 2mg/L,
Voriconazole 8 mg/LVoriconazole plasma concentration: 0.53 μg/mL < 1.0
Disseminated lesions in lung, pancreatic head, spleen, andkidney (CT 2).

Photo 2: Skin biopsy
Left (Grocott stain): Acute-angle
branching septate hyphae
Right (Culture result): Crescentshaped conidia

CT 2: Disseminated lesions of lung, pancreatic head, and spleen

Clinical course 3
Her condition improved with early discontinuation ofsteroids, increased voriconazole dose, and the additionof liposomal Amphotericin B. It was thought that
disseminated lesions might have become apparent
during the neutrophil recovery period. She had chronic
GVHD and received long-term prophylaxis(voriconazole) as secondary prevention after
completion of treatment.

In case of antimicrobial treatment not being successful
Even under immunocompromised conditions such as
severe neutropenia, antimicrobial therapy should bemodified based on assumptions about the causative
microorganism and infected organ.
In this case, if antifungals had been added or switchedwithout a biopsy of the skin lesion during theneutropenic phase, it would be difficult to confirm thediagnosis of disseminated fusariosis.
It’s very important to make every effort to diagnosecausative microorganisms and infected organs.
Fusariosis:
Unlike Aspergillus, the most common filamentous IFI,
candin antifungals are ineffective for fusariosis.
Appropriate treatment requires a definitive diagnosis.
Histological (morphological) differentiation from
Aspergillus is difficult and beta-d-glucan and Aspergillus
GM antigen can be positive, so culture tests areimportant for definitive diagnosis.
If treatment with antimicrobial treatment fails, it is important
to investigate the cause.

Examples of items to confirm
 Complication of new infectious diseases ormisdiagnosis of infectious disease- Check the spectrum of antimicrobial agents currently
being administered- Infections with few symptoms (e.g., catheterinfection, cholangitis) Incorrect antimicrobial dosage or administration- Confirmation of appropriate dosage, administration
method and blood concentration
 Infections that require surgical intervention- Abscesses, foreign bodies, necrotic foci, etc.
 Cases where it may take more time to improve evenwith appropriate treatment- Abscesses, intravascular infections, osteomyelitis,
severe immunodeficiencies, etc.
- Transient clinical exacerbation, such as infections
during neutrophil recovery or initial exacerbation at
the start of treatment
 Non-infectious diseases- Drug fever, neoplastic fever, aspiration, heart failure,etc.

This case study was compiled at the request of AMR Alliance Japan as part of a series of case studies designed to show actual cases in which antimicrobials were and were not used as examples of antimicrobial stewardship.
The patient consent has been obtained for the publication of this case.
For further information, contact AMR Alliance Japan (Secretariat: Health and Global Policy Institute), Grand Cube 3F, Otemachi Financial City, Global Business Hub Tokyo, 1-9-2, Otemachi, Chiyoda-ku, Tokyo, 100-0004 JAPAN Tel: +81-3-4243-7156 Fax: +81-3-4243-7378

E-mail: info@hgpi.org