| Type of infection |
Treatment recommendation |
Useful comments |
Candidaemia and deeply
invasive candidiasis |
First-line options approved by the FDA and/or the EMA:
Liposomal amphotericin B (3 mg/kg daily) [1]
Fluconazole (12 mg/kg daily) [2]
Caspofungin (day 1, 70 mg/m; 25 mg/m2 daily), [3] [4]
Micafungin (<40 kg, 2–4 mg/kg; ‡40 kg,
100–200 mg daily; in neonates recommend 10 mg/kg daily) [5]
Second-line options:
Amphotericin B lipid complex (5 mg/kg daily) [6]
Voriconazole (9 mg/kg/dose IV load day 1, then 8 mg/kg/dose or 9 mg/kg/dose PO maintainance. If >12 years, then load 6 mg/kg/dose and the 4 mg/kg/dose or give 200-300 mg PO per dose). *1
Treatment of other forms of invasive candidiasis
(endocarditis, peritonitis and meningitis) is ill-defined and based on pharmacological considerations such as a cidal mode of action and water solubility, and always includes the evaluation of surgical interventions. The additional use of flucytosine has a role in these situations. [7] [8] |
- Patients who have received azole prophylaxis, are
haemodynamically unstable or granulocytopenic, are
colonized with Candida glabrata or Candida krusei or
are admitted to institutions with a high frequency of
these organisms should receive a polyene or
echinocandin up front.
- Central venous catheters should be removed
promptly if feasible
- Neutropenic patients should receive
colony-stimulating factors, and in immunosuppressed
patients, steroids should be reduced, discontinued or replaced.
- The recommended duration of therapy for
uncomplicated candidaemia is 14 days after
clearance from the bloodstream and resolution of
all symptoms
- Following clearance from the bloodstream and
clinical stabilization, oral consolidation with
fluconazole is feasible for susceptible isolates
Fundoscopy is mandatory prior to end of treatment, to rule out endophthalmitis
|
| Invasive aspergillosis |
First-line options approved by the FDA and/or the
EMA:
Voriconazole (9 mg/kg/dose IV load day 1, then 8 mg/kg/dose or 9 mg/kg/dose PO maintainance. If >12 years, then load 6 mg/kg/dose and the 4 mg/kg/dose or give 200-300 mg PO per dose). *1
Second-line options:
Amphotericin B lipid complex (5 mg/kg daily) [9]
Caspofungin (50 mg/m2 daily; day 1,
[10]
Voriconazole is currently recommended for
Aspergillus terreus infections and infections affecting
the CNS [11]
In settings with a high frequency of mucormycosis,
voriconazole may not be a choice for pre-emptive
therapyDose escalation of liposomal amphotericin B to
10 mg/kg daily for the initial 14 days of treatment
was not beneficial in a randomized comparative trial
Combination of standard doses of either
voriconazole or liposomal amphotericin B with
caspofungin is promising, but valid clinical data are
currently lacking. [12] |
- Adjunctive surgical interventions need consideration
in skin and soft tissue infections, sinus infections,
impeding erosion of pulmonary arteries, and
operable CNS and lung lesions.
|
| Emerging fungal pathogens |
Amphotericin B is used as primary therapy for
mucormycosis; posaconazole has shown encouraging
clinical activity in the second-line setting.
Limited and uncontrolled data indicate an important
role of both voriconazole and posaconazole for
treatment of Scedosporium and Fusarium infections. [13][14] |
|
| Empirical antifungal therapy |
Options approved by the FDA and/or the EMA in
this indication:
Liposomal amphotericin B (1–3 mg/kg daily)
Caspofungin (50 mg/m2 daily; day 1,
70 mg/m2) [15] |
Empirical antifungal therapy is an established standard
of care in haemato-oncological patients with
prolonged neutropenia (ANC <500 for ‡10 days)
and refractory or new fever that provides targeted
prevention in a high-risk setting |
| Antifungal prophylaxis |
Prophylactic fluconazole (8–12 mg/kg daily) remains a
standard for post-allogeneic haematopoietic stem cell
transplantation; alternatives may include the use of
voriconazole or micafungin (1 mg/kg daily) [16]
In patients with GVHD and increased
immunosuppression, posaconazole (200 mg three
times daily) has been shown to prevent IFIs antinvasive aspergillosis. [17]
In adults with AML/MDS, posaconazole (200 mg
three times daily) had a significant impact on the
frequency of IFIs and, in particular, invasive
aspergillosis, coupled with an overall survival benefit. [18] |
Posaconazole may be given to children >12 years
with high-risk haematological malignancies, or used
for augmented immunosuppression for GVHD and
voriconazole in younger children. Alternatives
include liposomal amphotericin B (1 mg/kg
every other day) or micafungin (1 mg/kg daily) |
Prophylaxis in very low
birthweight preterm
neonates |
Four randomized controlled trials, including a
multicentre study, consistently reported significant
decreases in colonization and infection by Candida
spp. in the treated infants. On pooling of the
results, fluconazole reduced IFI risk by 75%, and all-cause mortality by 24%. [19] [20] [21] [22] |
Fluconazole may be given as antifungal prophylaxis in
institutions with a substantial incidence (>5% to
10%) of invasive candidiasis in very low birthweight
infants or in outbreak situations |
|
* Data taken from Groll & Trachianidis Clinical Microbiol Infect, 16, 1343-53, 2010
AML, acute myeloid leukaemia; ANC, absolute neutrophile count; CNS, central nervous system; EMA, European Medicines Agency; FDA, Food and Drug Administration;
G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte–macrophage colony-stimulating factor; GVHD, graft-versus-host disease; IFI, invasive fungal infection;
MDS, myelodysplastic syndrome.
(*Modified from Dornbusch et al. Pediatr Infect Dis J 28:734-7, 2009, and Groll & Tragiannidis CMI 16, 1343, 2010. For details on the selected treatment options, please consult original publication).
*1 W. Steinbach, personal communication.
|
