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Fungal Infections
trachea and abdominal infection. Eleven patients had undergone surgical debridement in 64 subjects occurred prior to (38 of 64), during
HSCT, four had diabetes mellitus, four had solid-organ transplants and (nine of 64) or both prior to and during (17 of 64) posaconazole
another five were suffering from haematological malignancies. Nine therapy. The success rate was similar for patients who did (61%) and
subjects (38%), before the diagnosis or zygomycosis had received did not (62%) undergo adjunctive surgical procedures. Importantly,
antifungal prophylaxis with another azole. Zygomycetes were isolated success was seen for 72.7% of patients with zygomycosis in the
from 17 patients (Rhizopus six, Mucor six, Cunninghamella three and brain, indicating the ability of posaconazole to penetrate the brain
Rhizomucor two). Overall, 19 patients (79%) had complete (11) or parenchyma. A total of 35 subjects (38%) died while receiving
partial (eight) response. It should be pointed out that for all patients posaconazole therapy or within one month of follow-up; 15 of deaths
who responded to therapy the underlying illness had improved or (43%) were attributed to zygomycosis. Death was seen primarily in
resolved, whereas failure was associated with progression of the subjects treated for <30 days, reflecting the aggressive nature of this
underlying disease and less than 31 days of posaconazole therapy. infection rather than the effect of posaconazole therapy. The authors
Nine patients died during therapy, two from persistent infection. For concluded their experience by indicating that: “The overall high success
18 patients who also underwent surgery, only two had a failed and survival rates provide encouraging data regarding posaconazole as
outcome. Surgery correlated with a 5.7 times higher chance of an alternative therapy for zygomycosis”.
survival, whereas a disseminated infection was 27 times more likely to
end in failure. Aspergillosis
Walsh et al.
13
in the effort to evaluate posaconazole in the treatment
In a retrospective study van Burik et al.
12
reported on 91 patients with of invasive aspergillosis between 1999 and 2001 conducted an open-
proven (n=69) or probable (n=22) zygomycosis. Data were collected label, multicentre study in 107 patients refractory to at least seven days
after sending a questionnaire to physicians who treated patients under of antifungal therapy (n=94) or intolerant to conventional therapy
(n=13). As a comparative reference group, information collected from
external control cases (n=86) was used. Haematological malignancies
(74%) were the most common underlying condition (allogeneic in
Surgery correlated with a 5.7 times
45%). Neutropoenia and previous use of steroids were the risk factors
higher chance of survival, whereas a in 20 and 73% of subjects, respectively. Aspergillosis involved the lung
disseminated infection was 27 times
in 74% of cases, being disseminated in 8%. Duration of therapy
extended to 372 days.
more likely to end in failure.
The overall success rate was 42% for posaconazole and 26% for
control subjects (p=0.006), with the efficacy of posaconazole appearing
a compassionate-use protocol between August 2001 and November as early as 30 days. The overall response was similar to other salvage
2004. Enrolled patients were given posaconazole because of either studies for invasive aspergillosis, including AMB lipid complex (42%),
disease progression or failure to improve after a seven-day course of caspofungin (45%) and voriconazole (38%). A. fumigatus, A. flavus
standard antifungal therapy (refractory infection) or because they were and A. terreus represented the most commonly isolated species with
intolerant to prior antifungal agents. Infection was documented by successful response rates to posaconazole of 41, 53 and 29%,
culture in 60, by histology in eight and by both methods in 23. Most respectively. Authors concluded that: ”Posaconazole is an alternative to
patients had one site of infection (61%), while in 39% ≥1 site was salvage therapy for patients with invasive aspergillosis who are
found. The distribution of infection sites was as follows: sinuses 42, refractory or intolerant to previous antifungal therapy”. Posaconazole,
pulmonary 37, cutaneous 13, brain 11, orbital 11, palate seven, which as voriconazole is active in vitro against A. terreus, a strain
gastrointestinal two and liver one). resistant as a rule to AMB, was used as salvage therapy in nine patients
who failed previous therapy with a lipid formulation of AMB.
14
Four of
Approximately 80% had received antifungal prophylaxis (20% them responded successfully; however, due to the small number of
voriconasole). Diabetes mellitus, haematological malignancies, patients, a conclusion cannot be drawn.
neutropoenia, GVHD and receipt of chronic steroid therapy were the
most frequent predisposing conditions. Absidia, Cunninghamella, Fusariosis
Mucor, Rhizomucor and Rhizopus spp. were the underlying pathogen After Aspergillus, Fusarium species are among the leading fungal
in two, eight, 17, seven and 25 patients, respectively. Posaconazole pathogens, causing fulminant IFI with mortality and failure rates ≥70%
was given for at least 30 days (range six to 1,005 days). Overall success when AMB is given.
15
Posaconazole is active in vitro against
(complete and partial response) was 60% (14% expressed a complete Fusarium,
6,7
whereas in pre-clinical animal studies the efficacy of the
response, 46% a partial response), 21% had stable disease and 17% new azole in the treatment of invasive fusaciosis has been
experienced treatment failure. It should be pointed out that 13 heavily demonstrated.
16
Raad et al.
15
were the first investigators to report on
immunosuppressed subjects who were treated for more than one salvage therapy for invasive fusariosis in 21 patients with risk factors
week with combined posaconazole and lipid formulations of AMB had such as haematological malignancies (n=16), HSCT (n=6), solid-organ
an overall response rate similar to that of patients who were treated transplantation (n=2) and diabetes (n=6). In 17 the reason for
with posaconazole monotherapy. enrolment was refractory infection and in four intolerance to previous
therapy. The site of infection was the lung in four, extrapulmonary in
Success rates were similar regardless of infection site, predisposing seven and disseminated in 10 patients. In 18 subjects Fusarium
conditions, reason for enrolment and infecting species. Adjunctive infection was proved and in three was characterised as probable.
82 EUROPEAN INFECTIOUS DISEASE 2007
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