Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

suitable for surgery

1st line – surgery

Back
ACUTE
|
suitable for surgery
1st line – 

surgery

Surgery is key to remove necrotic tissue and curb spread of infection. Necrosis occurs due to vascular thrombosis, which precludes adequate delivery of antifungal agents.[3]​ Surgery plays a vital role in all forms of mucormycosis whenever feasible.

In patients with rhino-orbito-cerebral mucormycosis, extensive surgical debridement frequently requires removal of the paranasal sinuses along with disease from the nose and the orbit, if involved.[55]

In patients with isolated cutaneous disease due to burns or in trauma patients, aggressive surgical debridement to remove all necrotic tissue is essential.

Plus – intravenous antifungal induction therapy

Back
ACUTE
|
suitable for surgery
Plus – 

intravenous antifungal induction therapy

Treatment recommended for ALL patients in selected patient group

Amphotericin-B is recommended first line.[12] Amphotericin-B belongs to the polyene class of antifungals and is the most effective therapy against agents of mucormycosis. Liposomal or lipid formulations are preferred over the deoxycholate formulation as they minimise renal dysfunction, infusion reactions, and toxicity.[12] Amphotericin-B deoxycholate is effective but should be avoided; its use is limited by substantial toxicity in the doses and treatment durations needed for mucormycosis. It should only be used in settings where no other antifungal treatment options are available.[12]

Posaconazole or isavuconazole are azole antifungals and may be used intravenously as a second-line treatment. They are the preferred treatments in patients with pre-existing renal compromise as amphotericin-B can cause nephrotoxicity, even lipid or liposomal formulations.[12]

Isavuconazole is approved in some countries for the treatment of invasive mucormycosis. It has less nephrotoxic potential than other intravenous azoles.[57] No therapeutic drug monitoring is needed.​

Posaconazole requires about 1 week to reach steady-state serum concentrations and should not be the initial therapy for a patient with mucormycosis.[58][59]​ Routine therapeutic drug monitoring is recommended with a trough level of >1 mg/L.[1]

Amphotericin-B is associated with nephrotoxicity, hypokalaemia, anaemia, and infusion-related adverse reactions. Azole antifungals are hepatotoxic (monitor liver function during therapy) and undergo a number of potential drug-drug interactions.

Combination antifungal therapy may be used in select patients (e.g., immunocompromised) under specialist guidance. However, there is a lack of evidence of clear benefit and an increased risk of toxicity.[12]

Initial treatment regimens are presented here. These regimens depend on the geographical location as not all recommended treatments have regulatory approval in all regions or are available for use in all clinical settings.[12]

Duration of therapy depends on clinical response and resolution of any immune defect; weeks to months of therapy are typically required. Consult an infectious disease specialist for further guidance on when to transition to oral therapy, or taper or stop therapy.[12]

Consult an infectious disease specialist if disease is progressive.[12]

Primary options

amphotericin B liposomal: 5-10 mg/kg intravenously every 24 hours

More

OR

amphotericin B lipid complex: 5-10 mg/kg intravenously every 24 hours

More

Secondary options

posaconazole: 300 mg intravenously every 12 hours for 2 doses, followed by 300 mg every 24 hours

OR

isavuconazole: 200 mg intravenously every 8 hours for 6 doses, followed by 200 mg every 24 hours

Plus – specific management of underlying medical problem

Back
ACUTE
|
suitable for surgery
Plus – 

specific management of underlying medical problem

Treatment recommended for ALL patients in selected patient group

In patients with diabetes mellitus reversal of acidosis is essential.

In transplant recipients (solid organ/stem cell), discontinuing or reducing immunosuppressive agents such as corticosteroids and chemotherapy whenever feasible is encouraged.[3]​ Granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon gamma may be beneficial by reversing therapy-induced neutropenia.[2]​ In haematology patients with mucormycosis and ongoing neutropenia, G-CSF has been used as an adjunct to antifungal therapy in several small patient cohorts.[12]​ Several case reports suggest that interferon gamma may be an effective treatment, including a case of abdominal mucormycosis unresponsive to conventional therapy that improved with nivolumab and interferon gamma.[62]​ Interferon gamma was also successfully used in an immunocompetent patient with invasive cutaneous mucormycosis after severe burns, leading to rapid clinical improvement and immune recovery.[63]​ However, adequate controlled trials are lacking.[3]​​

Patients with iron overload who are treated with desferrioxamine as an iron chelator should be switched to a suitable alternative iron chelator (e.g., deferiprone, deferasirox).[64]

Consider – oral antifungal maintenance therapy

Back
ACUTE
|
suitable for surgery
Consider – 

oral antifungal maintenance therapy

Additional treatment recommended for SOME patients in selected patient group

Further antifungal therapy depends on the initial clinical response and whether the patient experiences toxicity from the initial treatment regimens.

Once the patient is stable or has a partial response, either continue the first-line regimen or change to a suitable oral regimen.[12]

Oral isavuconazole or posaconazole are the preferred options for step-down treatment. The delayed-release tablet formulation of posaconazole is preferred to the suspension due to suboptimal bioavailability of the suspension.[12]

Azole antifungals are hepatotoxic (monitor liver function during therapy) and undergo a number of potential drug-drug interactions.

Duration of therapy depends on clinical response and resolution of any immune defect; weeks to months of therapy are typically required. Consult an infectious disease specialist for further guidance on when to taper or stop therapy.[12]

Primary options

posaconazole: 300 mg orally (delayed-release tablet) twice daily for 2 doses, followed by 300 mg once daily

More

OR

isavuconazole: 200 mg orally every 8 hours for 6 doses, followed by 200 mg every 24 hours

More

unsuitable for surgery

1st line – intravenous antifungal induction therapy

Back
ACUTE
|
unsuitable for surgery
1st line – 

intravenous antifungal induction therapy

Some patients may be too unwell to undergo surgery and these patients should receive antifungal therapy first line.[12]

Amphotericin-B is recommended first line.[12] Amphotericin-B belongs to the polyene class of antifungals and is the most effective therapy against agents of mucormycosis. Liposomal or lipid formulations are preferred over the deoxycholate formulation as they minimise renal dysfunction, infusion reactions, and toxicity.[12] Amphotericin-B deoxycholate is effective but should be avoided; its use is limited by substantial toxicity in the doses and treatment durations needed for mucormycosis. It should only be used in settings where no other antifungal treatment options are available.[12]

Posaconazole or isavuconazole are azole antifungals and may be used intravenously as a second-line treatment. They are the preferred treatments in patients with pre-existing renal compromise as amphotericin-B can cause nephrotoxicity, even lipid or liposomal formulations.[12]

Isavuconazole is approved in some countries for the treatment of invasive mucormycosis. It has less nephrotoxic potential than other intravenous azoles.[57] No therapeutic drug monitoring is needed.​

Posaconazole requires about 1 week to reach steady-state serum concentrations and should not be the initial therapy for a patient with mucormycosis.[58][59] Routine therapeutic drug monitoring is recommended with a trough level of >1 mg/L.[1]​​

Amphotericin-B is associated with nephrotoxicity, hypokalaemia, anaemia, and infusion-related adverse reactions. Azole antifungals are hepatotoxic (monitor liver function during therapy) and undergo a number of potential drug-drug interactions.

Combination antifungal therapy may be used in select patients (e.g., immunocompromised) under specialist guidance. However, there is a lack of evidence of clear benefit and an increased risk of toxicity.[12]

Initial treatment regimens are presented here. These regimens depend on the geographical location as not all recommended treatments have regulatory approval in all regions or are available for use in all clinical settings.[12] Duration of therapy depends on clinical response.

Duration of therapy depends on clinical response and resolution of any immune defect; weeks to months of therapy are typically required. Consult an infectious disease specialist for further guidance on when to transition to oral therapy, or taper or stop therapy.[12]

Consult an infectious disease specialist if disease is progressive.[12]

Primary options

amphotericin B liposomal: 5-10 mg/kg intravenously every 24 hours

More

OR

amphotericin B lipid complex: 5-10 mg/kg intravenously every 24 hours

More

Secondary options

posaconazole: 300 mg intravenously every 12 hours for 2 doses, followed by 300 mg every 24 hours

OR

isavuconazole: 200 mg intravenously every 8 hours for 6 doses, followed by 200 mg every 24 hours

Plus – specific management of underlying medical problem

Back
ACUTE
|
unsuitable for surgery
Plus – 

specific management of underlying medical problem

Treatment recommended for ALL patients in selected patient group

In patients with diabetes mellitus reversal of acidosis is essential.

In transplant recipients (solid organ/stem cell), discontinuing or reducing immunosuppressive agents such as corticosteroids and chemotherapy whenever feasible is encouraged.[3]​ Granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon gamma may be beneficial by reversing therapy-induced neutropenia.[2]​ In haematology patients with mucormycosis and ongoing neutropenia, G-CSF has been used as an adjunct to antifungal therapy in several small patient cohorts.[12]​ Several case reports suggest that interferon gamma may be an effective treatment, including a case of abdominal mucormycosis unresponsive to conventional therapy that improved with nivolumab and interferon gamma.[62]​ Interferon gamma was also successfully used in an immunocompetent patient with invasive cutaneous mucormycosis after severe burns, leading to rapid clinical improvement and immune recovery.[63]​ However, adequate controlled trials are lacking.[3]​​

Patients with iron overload who are treated with desferrioxamine as an iron chelator should be switched to a suitable alternative iron chelator (e.g., deferiprone, deferasirox).[64]

Consider – oral antifungal maintenance therapy

Back
ACUTE
|
unsuitable for surgery
Consider – 

oral antifungal maintenance therapy

Additional treatment recommended for SOME patients in selected patient group

Further antifungal therapy depends on the initial clinical response and whether the patient experiences toxicity from the initial treatment regimens.

Once the patient is stable or has a partial response, either continue the first-line regimen or change to a suitable oral regimen.[12]

Oral isavuconazole or posaconazole are the preferred options for step-down treatment. The delayed-release tablet formulation of posaconazole is preferred to the suspension due to suboptimal bioavailability of the suspension.​[12]

Azole antifungals are hepatotoxic (monitor liver function during therapy) and undergo a number of potential drug-drug interactions.

Duration of therapy depends on clinical response and resolution of any immune defect; weeks to months of therapy are typically required. Consult an infectious disease specialist for further guidance on when to taper or stop therapy.[12]

Primary options

posaconazole: 300 mg orally (delayed-release tablet) twice daily for 2 doses, followed by 300 mg once daily

More

OR

isavuconazole: 200 mg orally every 8 hours for 6 doses, followed by 200 mg every 24 hours

More
ONGOING

treatment failure

1st line – salvage antifungal therapy

Back
ONGOING
|
treatment failure
1st line – 

salvage antifungal therapy

Salvage antifungal therapy is recommended in patients with treatment failure (i.e., due to refractory mucormycosis or toxicity/intolerance to first-line regimens). The choice of drug for salvage therapy depends on the drug used initially. As only two drug classes are recommended for mucormycosis, salvage therapy typically involves switching to the other drug class.[12]

Salvage therapy with isavuconazole or posaconazole can be considered in patients who do not respond to, or experience toxicity with, initial treatment with amphotericin-B. Liposomal amphotericin-B, and amphotericin-B lipid, complex are suitable salvage options for cases of primary treatment failure with azole antifungals.[12]

Amphotericin-B is associated with nephrotoxicity, hypokalaemia, anaemia, and infusion-related adverse reactions. Azole antifungals are hepatotoxic (monitor liver function during therapy) and undergo a number of potential drug-drug interactions.

Combination antifungal therapy may be used in select patients under specialist guidance. However, there is a lack of evidence of clear benefit and an increased risk of toxicity.[12]

Duration of therapy depends on clinical response and resolution of any immune defect; weeks to months of therapy are typically required. Consult an infectious disease specialist for further guidance on when to transition to oral therapy, or taper or stop therapy.[12]

Primary options

amphotericin B liposomal: 5-10 mg/kg intravenously every 24 hours

More

OR

amphotericin B lipid complex: 5-10 mg/kg intravenously every 24 hours

More

OR

posaconazole: 300 mg intravenously/orally (delayed-release tablet) every 12 hours for 2 doses, followed by 300 mg every 24 hours

OR

isavuconazole: 200 mg intravenously/orally every 8 hours for 6 doses, followed by 200 mg every 24 hours

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer