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

INITIAL

active non-life-threatening infection: on first presentation

1st line – empiric broad-spectrum antibiotic therapy

Back
INITIAL
|
active non-life-threatening infection: on first presentation
1st line – 

empiric broad-spectrum antibiotic therapy

Procedures to aid in identification of the infecting organism, such as surgical biopsy of infected sites or bronchoalveolar lavage, are recommended before treatment if available.

Initial treatment is broad, including coverage of Staphylococcus aureus as well as gram-negative organisms.

Systemic fluoroquinolone antibiotics (e.g., ciprofloxacin, levofloxacin, moxifloxacin) may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[89] ​Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Infections include pneumonia, cutaneous and soft tissue infections, adenitis, internal abscesses, and osteomyelitis.[3][16][39][52]

Once the organism is identified, directed therapy may be initiated. Early consultation with physicians experienced in the care of CGD is recommended.

Primary options

meropenem: adults: 1 g every 8 hours

OR

levofloxacin: adults: 750 mg intravenously every 24 hours

OR

ciprofloxacin: adults: 200-400 mg intravenously every 12 hours

OR

moxifloxacin: adults: 400 mg intravenously every 24 hours

OR

chloramphenicol: adults: 50-100 mg/kg/day intravenously given in divided doses every 6 hours

OR

cefotaxime: children: 100-200 mg/kg/day intravenously given in divided doses every 8 hours; adults: 1-2 g intravenously every 6-8 hours

OR

ceftriaxone: children: 50-100 mg/kg/day intravenously given in divided doses every 12-24 hours; adults: 1-2 g intravenously every 24 hours

Plus – broad-spectrum antifungal therapy

Back
INITIAL
|
active non-life-threatening infection: on first presentation
Plus – 

broad-spectrum antifungal therapy

Treatment recommended for ALL patients in selected patient group

Early broad antifungal coverage is often needed as well, specifically for Aspergillus species. Voriconazole, posaconazole, or liposomal amphotericin-B are the agents of choice; itraconazole is an alternative option, although use is not recommended if a patient takes this as prophylaxis.[58][59][60]

Early consultation with physicians experienced in the care of CGD is recommended.

Primary options

amphotericin B liposomal: children and adults: 3-5 mg/kg intravenously every 24 hours

OR

voriconazole: children ≥2 years of age: 9 mg/kg intravenously every 12 hours on day 1, followed by 8 mg/kg every 12 hours, maximum 700 mg/day; adults: 6 mg/kg intravenously every 12 hours on day 1, followed by 4 mg/kg every 12 hours

OR

posaconazole: adults: 300 mg orally (delayed-release)/intravenously twice daily on day 1, followed by 300 mg once daily; 200 mg orally (suspension) three times daily

Secondary options

itraconazole: children: 5-10 mg/kg/day orally given in 1-2 divided doses, maximum 400 mg/day; adults: 200-400 mg/day orally given in 1-2 divided doses

More

active life-threatening infection: on first presentation

1st line – empiric broad-spectrum antibiotic therapy

Back
INITIAL
|
active life-threatening infection: on first presentation
1st line – 

empiric broad-spectrum antibiotic therapy

Initial treatment is broad, including coverage of Staphylococcus aureus as well as gram-negative organisms.

Systemic fluoroquinolone antibiotics (e.g., ciprofloxacin, levofloxacin, moxifloxacin) may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[89]​ Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Infections include pneumonia, cutaneous and soft tissue infections, adenitis, internal abscesses, and osteomyelitis.[3][16][39][52]

Once the organism is identified, directed therapy may be initiated. Early consultation with physicians experienced in the care of CGD is recommended.

Primary options

meropenem: adults: 1 g every 8 hours

OR

levofloxacin: adults: 750 mg intravenously every 24 hours

OR

ciprofloxacin: adults: 200-400 mg intravenously every 12 hours

OR

moxifloxacin: adults: 400 mg intravenously every 24 hours

OR

chloramphenicol: adults: 50-100 mg/kg/day intravenously given in divided doses every 6 hours

OR

cefotaxime: children: 100-200 mg/kg/day intravenously given in divided doses every 8 hours; adults: 1-2 g intravenously every 6-8 hours

OR

ceftriaxone: children: 50-100 mg/kg/day intravenously given in divided doses every 12-24 hours; adults: 1-2 g intravenously every 24 hours

Plus – broad-spectrum antifungal therapy

Back
INITIAL
|
active life-threatening infection: on first presentation
Plus – 

broad-spectrum antifungal therapy

Treatment recommended for ALL patients in selected patient group

Early broad-spectrum antifungal coverage is needed as well, specifically for Aspergillus species. Voriconazole, posaconazole, or liposomal amphotericin-B are the agents of choice; itraconazole is an alternative option, although use is not recommended if a patient takes this as prophylaxis.[58][59][60]

Early consultation with physicians experienced in the care of CGD is recommended.

Primary options

amphotericin B liposomal: children and adults: 3-5 mg/kg intravenously every 24 hours

OR

voriconazole: children ≥2 years of age: 9 mg/kg intravenously every 12 hours on day 1, followed by 8 mg/kg every 12 hours, maximum 700 mg/day; adults: 6 mg/kg intravenously every 12 hours on day 1, followed by 4 mg/kg every 12 hours

OR

posaconazole: adults: 300 mg orally (delayed-release)/intravenously twice daily on day 1, followed by 300 mg once daily; 200 mg orally (suspension) three times daily

Secondary options

itraconazole: children: 5-10 mg/kg/day orally given in 1-2 divided doses, maximum 400 mg/day; adults: 200-400 mg/day orally given in 1-2 divided doses

More

Consider – granulocyte transfusion

Back
INITIAL
|
active life-threatening infection: on first presentation
Consider – 

granulocyte transfusion

Treatment recommended for SOME patients in selected patient group

Granulocyte transfusions may be administered as a "last resort" for life-threatening infections.[61][62][63][64][65][50]

The short-term benefits of providing functional granulocytes should be weighed against the risk from exposure to foreign antigens (e.g., HLA antigens).

Consider – interferon gamma

Back
INITIAL
|
active life-threatening infection: on first presentation
Consider – 

interferon gamma

Treatment recommended for SOME patients in selected patient group

The use of interferon gamma in the treatment of infections in CGD patients remains poorly studied and controversial, although some experts support its use in severely ill patients in the hope of providing benefit.[41]

Primary options

interferon gamma 1b: children and adults: consult specialist for guidance on dose

Consider – surgical or radiological drainage

Back
INITIAL
|
active life-threatening infection: on first presentation
Consider – 

surgical or radiological drainage

Treatment recommended for SOME patients in selected patient group

Surgical or radiological drainage of infected tissue may be required.

ACUTE

following initial empiric treatment

1st line – continued empiric broad-spectrum antibiotic therapy

Back
ACUTE
|
following initial empiric treatment
|
pyogenic hepatic abscess
1st line – 

continued empiric broad-spectrum antibiotic therapy

Treatment is broad-spectrum antibiotic therapy, including coverage of Staphylococcus aureus as well as gram-negative organisms.

Systemic fluoroquinolone antibiotics (e.g., ciprofloxacin, levofloxacin, moxifloxacin) may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[89]​ Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Early consultation with physicians experienced in the care of CGD is recommended.

Primary options

meropenem: adults: 1 g every 8 hours

OR

levofloxacin: adults: 750 mg intravenously every 24 hours

OR

ciprofloxacin: adults: 200-400 mg intravenously every 12 hours

OR

moxifloxacin: adults: 400 mg intravenously every 24 hours

OR

chloramphenicol: adults: 50-100 mg/kg/day intravenously given in divided doses every 6 hours

OR

cefotaxime: children: 100-200 mg/kg/day intravenously given in divided doses every 8 hours; adults: 1-2 g intravenously every 6-8 hours

OR

ceftriaxone: children: 50-100 mg/kg/day intravenously given in divided doses every 12-24 hours; adults: 1-2 g intravenously every 24 hours

Plus – corticosteroid

Back
ACUTE
|
following initial empiric treatment
|
pyogenic hepatic abscess
Plus – 

corticosteroid

Treatment recommended for ALL patients in selected patient group

Hepatic abscesses are treated with antibiotics in conjunction with a corticosteroid.[66][67]

Primary options

methylprednisolone sodium succinate: children and adults: 1 mg/kg/day intravenously, taper slowly after clinical response achieved

Consider – broad-spectrum antifungal therapy

Back
ACUTE
|
following initial empiric treatment
|
pyogenic hepatic abscess
Consider – 

broad-spectrum antifungal therapy

Treatment recommended for SOME patients in selected patient group

Early broad-spectrum antifungal coverage may be needed as well, specifically for Aspergillus species.

Early consultation with physicians experienced in the care of CGD is recommended.

Primary options

amphotericin B liposomal: children and adults: 3-5 mg/kg intravenously every 24 hours

OR

voriconazole: children ≥2 years of age: 9 mg/kg intravenously every 12 hours on day 1, followed by 8 mg/kg every 12 hours, maximum 700 mg/day; adults: 6 mg/kg intravenously every 12 hours on day 1, followed by 4 mg/kg every 12 hours

OR

posaconazole: adults: 300 mg orally (delayed-release)/intravenously twice daily on day 1, followed by 300 mg once daily; 200 mg orally (suspension) three times daily

Secondary options

itraconazole: children: 5-10 mg/kg/day orally given in 1-2 divided doses, maximum 400 mg/day; adults: 200-400 mg/day orally given in 1-2 divided doses

More

Consider – granulocyte injection ± interferon-gamma

Back
ACUTE
|
following initial empiric treatment
|
pyogenic hepatic abscess
Consider – 

granulocyte injection ± interferon-gamma

Treatment recommended for SOME patients in selected patient group

The use of normal donor granulocytes injected into lesions has been reported, as well as systemic granulocyte infusions and interferon-gamma administration.[68]

Consider – surgical incision and drainage

Back
ACUTE
|
following initial empiric treatment
|
pyogenic hepatic abscess
Consider – 

surgical incision and drainage

Treatment recommended for SOME patients in selected patient group

Definitive surgical excision and drainage should be considered in patients not responding to antibiotic and corticosteroid therapy.[50] Samples should be taken in all cases to identify the pathogen and guide treatment. Staphylococcus aureus is typically the etiology.[12] Percutaneous drainage may be helpful. Systemic antibiotic and antifungal treatment is recommended postoperatively in those undergoing surgery.

1st line – corticosteroid

Back
ACUTE
|
following initial empiric treatment
|
inflammatory enterocolitis
1st line – 

corticosteroid

Can be used to treat granulomatous inflammatory lesions, reducing gastrointestinal symptoms in severe disease and flares.

Primary options

prednisone: children: 1 mg/kg orally once daily initially, taper according to response; adults: 5-60 mg orally once daily, taper according to response

1st line – sulfasalazine

Back
ACUTE
|
following initial empiric treatment
|
inflammatory enterocolitis
1st line – 

sulfasalazine

Aids in reducing colonic inflammation in mild disease.

Other more potent immunosuppressive agents may also be used.

Primary options

sulfasalazine: children: 50 mg/kg/day orally given in divided doses every 6 hours; adults: 500 mg orally four times daily; occasionally higher doses may be required

1st line – continued empiric broad-spectrum antibiotic therapy

Back
ACUTE
|
following initial empiric treatment
|
infectious enterocolitis
1st line – 

continued empiric broad-spectrum antibiotic therapy

Treatment is broad-spectrum, including coverage of common enteric pathogens according to local sensitivities.

Systemic fluoroquinolone antibiotics (e.g., ciprofloxacin) may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[89]​ Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Early consultation with physicians experienced in the care of CGD is recommended.

Primary options

ciprofloxacin: adults: 200-400 mg intravenously every 12 hours

OR

ceftriaxone: children: 50-100 mg/kg/day intravenously given in divided doses every 12-24 hours; adults: 1-2 g intravenously every 24 hours

1st line – corticosteroid

Back
ACUTE
|
following initial empiric treatment
|
gastrointestinal or genitourinary obstruction
1st line – 

corticosteroid

Most obstructions of hollow viscera can be managed with corticosteroids.

Primary options

prednisone: children: 1 mg/kg orally once daily initially, taper according to response; adults: 30-60 mg orally once daily, taper according to response

Consider – surgery

Back
ACUTE
|
following initial empiric treatment
|
gastrointestinal or genitourinary obstruction
Consider – 

surgery

Treatment recommended for SOME patients in selected patient group

Surgery is indicated for nonresolving obstruction or severe fistulae.[6][8][11]

ONGOING

following resolution of acute episode

1st line – maintenance antibiotic prophylaxis plus vigilant monitoring for infection

Back
ONGOING
|
following resolution of acute episode
1st line – 

maintenance antibiotic prophylaxis plus vigilant monitoring for infection

In the absence of active infections requiring immediate attention, timely referral to a specialist with experience in the management of patients with CGD is warranted.

Prophylaxis with antibiotics should begin promptly with trimethoprim/sulfamethoxazole or other similar medications effective against Staphylococcus aureus and gram-negative organisms. An additional agent may be required to cover methicillin-resistant S aureus if prevalent.

Systemic fluoroquinolone antibiotics (e.g., ciprofloxacin) may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[89]​ Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Primary options

sulfamethoxazole/trimethoprim: children and adults: 5 mg/kg orally once or twice daily

More

Secondary options

ciprofloxacin: adults: 250-500 mg orally twice daily

OR

trimethoprim: adults: 100 mg orally once daily at bedtime

OR

cefuroxime axetil: adults: 250-500 mg orally twice daily

OR

cefixime: adults: 400 mg orally once daily

OR

cefpodoxime proxetil: adults: 100-400 mg orally twice daily

Plus – maintenance antifungal prophylaxis

Back
ONGOING
|
following resolution of acute episode
Plus – 

maintenance antifungal prophylaxis

Treatment recommended for ALL patients in selected patient group

Antifungal prophylaxis with itraconazole has become the standard of care for patients with CGD and is shown to decrease the incidence of fungal infection.[71] Aspergillus infections have been the most common cause of death in patients with CGD, although this is changing with widespread use of antifungal prophylaxis.[3][13][16]

If itraconazole is not tolerated, choose an alternative antifungal prophylactic medication that is effective against Aspergillus species.

Voriconazole is an oral alternative, but it carries the risk of reversible liver damage, photosensitivity, and cutaneous malignancy.[58][59][72]

Posaconazole has been used for salvage therapy in patients, although this restricts treatment options for breakthrough infection.[73]

Serum drug levels may be required in patients on azole antifungals.

Primary options

itraconazole: children: 2.5 mg/kg orally twice daily, maximum 200 mg/dose; adults: 200 mg orally twice daily

OR

voriconazole: children ≥2 years of age: 4 mg/kg orally twice daily, maximum 200 mg/dose; adults: 200 mg orally twice daily

OR

posaconazole: children ≥2 years of age and ≥40 kg body weight and adults: 300 mg orally (delayed-release) twice daily on day 1, followed by 300 mg once daily; children ≥13 years of age and adults: 200 mg orally (suspension) three times daily

Consider – maintenance interferon gamma therapy

Back
ONGOING
|
following resolution of acute episode
Consider – 

maintenance interferon gamma therapy

Treatment recommended for SOME patients in selected patient group

Interferon gamma decreases the incidence of infection, although study results are conflicting.[30][74][75][76][77]​​ One meta-analysis supports its use but the results are largely based on one randomized controlled trial from 1991.[78]​ The routine use of interferon gamma is highly variable even among specialists. In the US, interferon gamma is used and recommended by guidelines.[79]​ It is not routinely given in the UK and rest of Europe. Adverse effects limit usage.

Fever is a common adverse effect; however, the occurrence of fever in a patient with CGD always warrants medical evaluation.

Primary options

interferon gamma 1b: consult specialist for guidance on dose

Consider – evaluation for allogeneic stem cell transplant

Back
ONGOING
|
following resolution of acute episode
Consider – 

evaluation for allogeneic stem cell transplant

Treatment recommended for SOME patients in selected patient group

Allogeneic stem cell transplantation is a curative procedure, although it carries its own risks of mortality and morbidity particularly if undertaken later in life. Overall survival is greater than 80%, with the majority of surviving patients achieving cure, particularly if an HLA-matched donor is available.[80][81][82][83][84][85][86][87]​ Recent advances in critical care support and in carefully applied conditioning regimens are improving the mortality and morbidity for transplant patients, although outcomes vary across centers.[88]

Transplantation should be considered if a matched sibling donor is available.[50] Additionally, matched unrelated (including cord blood) donors should be considered appropriate sources for stem cells in children.

In adults, careful consideration must be given to the potential risks and benefits of stem cell transplantation; a large report found a 76% overall survival and 69% event-free survival at 3 years even in patients age 18 years and older.[87]​ Without transplant, prognosis is adversely affected by frequent complications including chronic respiratory disease, inflammatory bowel disease, a need for gastrointestinal surgery, and development of malignancy.[34]

Stem cell transplantation should be undertaken in medical centers experienced in transplantation for primary immunodeficiency disorders.

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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

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