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

necrotising fasciitis awaiting confirmation of microbial culture and sensitivity results

1st line – surgical debridement + intensive supportive care

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INITIAL
|
necrotising fasciitis awaiting confirmation of microbial culture and sensitivity results
1st line – 

surgical debridement + intensive supportive care

Surgical incisions should extend beyond the areas of visible necrosis and the entire necrotic area excised. Further surgical evaluation and debridement as necessary is essential and several procedures may be required.[17] Intensive haemodynamic support with intravenous infusion is an important aspect of surgical management.

Plus – empirical broad-spectrum antibiotics

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INITIAL
|
necrotising fasciitis awaiting confirmation of microbial culture and sensitivity results
Plus – 

empirical broad-spectrum antibiotics

Treatment recommended for ALL patients in selected patient group

For empirical treatment of type I mixed infections, the Infectious Diseases Society of America (IDSA) recommends agents effective against both aerobes (including MRSA) and anaerobes.[17] Options include vancomycin or linezolid combined with either: piperacillin/tazobactam; a carbapenem; ceftriaxone plus metronidazole; or a fluoroquinolone plus metronidazole. Penicillin plus clindamycin is recommended for treatment of suspected (or confirmed) group A streptococcal necrotising fasciitis.

For patients allergic to penicillin, clindamycin or metronidazole with an aminoglycoside or fluoroquinolone may be used.

When further information is available and aetiological agent has been determined, antibiotic therapy should be amended to target the specific agent.

As there are currently no definitive clinical trials, the IDSA recommends continuing antibiotics until no further surgical debridement is needed, the patient has improved clinically, and fever has been absent for 48 to 72 hours.[17]

In November 2018, the European Medicines Agency (EMA) completed a review of serious, disabling, and potentially irreversible adverse effects associated with systemic and inhaled fluoroquinolone antibiotics. These adverse effects include tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects. As a consequence of this review, the EMA now recommends that fluoroquinolone antibiotics be restricted for use in serious, life-threatening bacterial infections only. Furthermore, it recommends that fluoroquinolones should not be used for mild to moderate infections unless other appropriate antibiotics for the specific infection cannot be used, and should not be used in non-severe, non-bacterial, or self-limiting infections. Patients who are older, have renal impairment, or have had a solid organ transplant, and those being treated with a corticosteroid, are at a higher risk of tendon damage. Co-administration of a fluoroquinolone and a corticosteroid should be avoided.[49] The UK-based Medicines and Healthcare products Regulatory Agency (MHRA) supports these recommendations.[50] The US Food and Drug Administration (FDA) issued a similar safety communication in 2016, restricting the use of fluoroquinolones in acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections.[51] In addition to these restrictions, the FDA has issued warnings about the increased risk of aortic dissection, significant hypoglycaemia, and mental health adverse effects in patients taking fluoroquinolones.[52][53]

Primary options

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours

or

linezolid: 600 mg intravenously every 12 hours

-- AND --

piperacillin/tazobactam: 3.375 g intravenously every 6 hours

More

or

imipenem/cilastatin: 1 g intravenously every 6-8 hours

or

meropenem: 1 g intravenously every 8 hours

or

ertapenem: 1 g intravenously every 24 hours

OR

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours

or

linezolid: 600 mg intravenously every 12 hours

-- AND --

ceftriaxone: 1-2 g intravenously every 12-24 hours

or

ciprofloxacin: 400 mg intravenously every 12 hours

or

delafloxacin: 300 mg intravenously every 12 hours

-- AND --

metronidazole: 30 mg/kg/day intravenously given in divided doses every 6 hours

OR

benzylpenicillin sodium: 2.4 to 4.8 g/day intravenously given in divided doses every 4-6 hours

and

clindamycin: 600-900 mg intravenously every 8 hours

Secondary options

clindamycin: 600-900 mg intravenously every 8 hours

or

metronidazole: 30 mg/kg/day intravenously given in divided doses every 6 hours

-- AND --

gentamicin: 3-5 mg/kg/day intravenously given in divided doses every 8 hours

or

ciprofloxacin: 400 mg intravenously every 12 hours

or

delafloxacin: 300 mg intravenously every 12 hours

ACUTE

confirmed type I necrotising fasciitis (polymicrobial)

1st line – intensive supportive care + surgical debridement ± amputation

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ACUTE
|
confirmed type I necrotising fasciitis (polymicrobial)
1st line – 

intensive supportive care + surgical debridement ± amputation

Necrotising fasciitis is a surgical emergency, and the patient should be urgently taken to the operating room for debridement of all infected devitalised tissues. Amputation may be required.

Wide excision of all necrotic tissue, placement of drains, and appropriate surgical debridement are necessary for both diagnosis and treatment.[44] Further surgical evaluation and debridement as necessary is essential, and several procedures may be required.[17]

Intensive haemodynamic support with intravenous infusion is an important aspect of surgical management.

Plus – local irrigation with bacitracin-infused normal saline

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ACUTE
|
confirmed type I necrotising fasciitis (polymicrobial)
Plus – 

local irrigation with bacitracin-infused normal saline

Treatment recommended for ALL patients in selected patient group

Following surgical debridement, many surgeons use local irrigation with bacitracin-infused normal saline.

Plus – broad-spectrum intravenous antibiotics

Back
ACUTE
|
confirmed type I necrotising fasciitis (polymicrobial)
Plus – 

broad-spectrum intravenous antibiotics

Treatment recommended for ALL patients in selected patient group

For empirical treatment of type I mixed infections, the Infectious Diseases Society of America (IDSA) recommends agents effective against both aerobes (including MRSA) and anaerobes.[17] Options include vancomycin or linezolid combined with either: piperacillin/tazobactam; a carbapenem; ceftriaxone plus metronidazole; or a fluoroquinolone plus metronidazole.

For patients allergic to penicillin, clindamycin or metronidazole with an aminoglycoside or fluoroquinolone may be used.

When further information is available and aetiological agent has been determined, antibiotic therapy should be amended to target the specific agent.

As there are currently no definitive clinical trials, the IDSA recommends continuing antibiotics until no further surgical debridement is needed, the patient has improved clinically, and fever has been absent for 48 to 72 hours.[17]

In November 2018, the European Medicines Agency (EMA) completed a review of serious, disabling, and potentially irreversible adverse effects associated with systemic and inhaled fluoroquinolone antibiotics. These adverse effects include tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects. As a consequence of this review, the EMA now recommends that fluoroquinolone antibiotics be restricted for use in serious, life-threatening bacterial infections only. Furthermore, it recommends that fluoroquinolones should not be used for mild to moderate infections unless other appropriate antibiotics for the specific infection cannot be used, and should not be used in non-severe, non-bacterial, or self-limiting infections. Patients who are older, have renal impairment, or have had a solid organ transplant, and those being treated with a corticosteroid, are at a higher risk of tendon damage. Co-administration of a fluoroquinolone and a corticosteroid should be avoided.[49] The UK-based Medicines and Healthcare products Regulatory Agency (MHRA) supports these recommendations.[50] The US Food and Drug Administration (FDA) issued a similar safety communication in 2016, restricting the use of fluoroquinolones in acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections.[51] In addition to these restrictions, the FDA has issued warnings about the increased risk of aortic dissection, significant hypoglycaemia, and mental health adverse effects in patients taking fluoroquinolones.[52][53]

Primary options

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours

or

linezolid: 600 mg intravenously every 12 hours

-- AND --

piperacillin/tazobactam: 3.375 g intravenously every 6 hours

More

or

imipenem/cilastatin: 1 g intravenously every 6-8 hours

or

meropenem: 1 g intravenously every 8 hours

or

ertapenem: 1 g intravenously every 24 hours

OR

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours

or

linezolid: 600 mg intravenously every 12 hours

-- AND --

ceftriaxone: 1-2 g intravenously every 12-24 hours

or

ciprofloxacin: 400 mg intravenously every 12 hours

or

delafloxacin: 300 mg intravenously every 12 hours

-- AND --

metronidazole: 30 mg/kg/day intravenously given in divided doses every 6 hours

Secondary options

clindamycin: 600-900 mg intravenously every 8 hours

or

metronidazole: 30 mg/kg/day intravenously given in divided doses every 6 hours

-- AND --

gentamicin: 3-5 mg/kg/day intravenously given in divided doses every 8 hours

or

ciprofloxacin: 400 mg intravenously every 12 hours

or

delafloxacin: 300 mg intravenously every 12 hours

confirmed type II necrotising fasciitis (monomicrobial)

1st line – intensive supportive care + surgical debridement ± amputation

Back
ACUTE
|
confirmed type II necrotising fasciitis (monomicrobial)
1st line – 

intensive supportive care + surgical debridement ± amputation

Necrotising fasciitis is a surgical emergency, and the patient should be urgently taken to the operating room for debridement of all infected devitalised tissues.

Wide excision of all necrotic tissue, placement of drains, and appropriate surgical debridement are necessary for both diagnosis and treatment.[44] Further surgical evaluation and debridement as necessary is essential, and several procedures may be required.[17]

Intensive haemodynamic support with intravenous infusion is an important aspect of surgical management.

Plus – intravenous antibiotics

Back
ACUTE
|
confirmed type II necrotising fasciitis (monomicrobial)
Plus – 

intravenous antibiotics

Treatment recommended for ALL patients in selected patient group

Type II infections are most commonly caused by Group A Streptococcus (i.e., Streptococcus pyogenes), but can also be caused by MRSA. In addition to urgent surgical debridement, penicillin plus clindamycin should be administered to treat group A streptococci and inhibit their ability to synthesise toxins.[17]

Clindamycin has been shown to be superior to penicillin for treatment of experimentally induced necrotising fasciitis or myonecrosis caused by group A streptococci.[23] It has been shown to reduce the in vitro release of streptococcal pyrogenic exotoxin A; is not affected by inoculum size or stage of growth; facilitates phagocytosis of Streptococcus pyogenes by inhibiting M-protein synthesis; suppresses the production of regulatory elements that control cell wall synthesis; and it has a long post-antibiotic effect.[23]

If there is any question regarding the aetiological agent (e.g., possibly Staphylococcus aureus rather than a group A Streptococcus), nafcillin should be used in place of penicillin.[1]

For patients with penicillin allergy, vancomycin, daptomycin, or linezolid (if co-existent vancomycin allergy) as a monotherapy should be substituted in place of the penicillin-clindamycin or nafcillin-clindamycin combination.[17]

The Infectious Diseases Society of America (IDSA) recommends a combination of doxycycline plus either ceftriaxone or cefotaxime for necrotising fasciitis due to Vibrio vulnificus, or a combination of doxycycline plus either ceftriaxone or ciprofloxacin for Aeromonas hydrophila.[17]

Primary options

benzylpenicillin sodium: 2.4 to 4.8 g/day intravenously given in divided doses every 4-6 hours

and

clindamycin: 600-900 mg intravenously every 8 hours

OR

doxycycline: 100 mg intravenously every 12 hours

-- AND --

ceftriaxone: 1-2 g intravenously every 12-24 hours

or

cefotaxime: 2 g intravenously every 8 hours

or

ciprofloxacin: 400 mg intravenously every 12 hours

Secondary options

nafcillin: 1.5 to 2 g intravenously every 4-6 hours

and

clindamycin: 600-900 mg intravenously every 8 hours

OR

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours

OR

daptomycin: 4 mg/kg intravenously once daily

OR

linezolid: 600 mg intravenously every 12 hours

Consider – hyperbaric oxygen therapy

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ACUTE
|
confirmed type II necrotising fasciitis (monomicrobial)
Consider – 

hyperbaric oxygen therapy

Additional treatment recommended for SOME patients in selected patient group

Hyperbaric oxygen (HBO) therapy can be considered as adjuvant therapy after prompt debridement in patients with necrotising soft tissue infections if no improvement in clinical condition is seen.[12] It is delivered at 100% oxygen at 2 to 3 times atmospheric pressure. While no prospective randomised trials have been published, retrospective analysis has shown an improvement in mortality despite the higher hospitalisation cost and length of stay.[60] There remains a lack of high-quality, valid evidence for the effects of HBO therapy on wound healing. It should not delay prompt surgical exploration and/or empirical antibiotic therapy.

Consider – intravenous immunoglobulin (IVIG)

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ACUTE
|
confirmed type II necrotising fasciitis (monomicrobial)
|
streptococcal toxic shock
Consider – 

intravenous immunoglobulin (IVIG)

Additional treatment recommended for SOME patients in selected patient group

The addition of IVIG may also be considered for treatment of streptococcal toxic shock syndrome, although data on efficacy are conflicting.[12][17]

Primary options

normal immunoglobulin human: 1 g/kg intravenously on day 1, followed by 0.5 g/kg on days 2 and 3; or 2 g/kg intravenously as a single dose

More

gas gangrene

1st line – intensive supportive care+ surgical debridement ± amputation

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ACUTE
|
gas gangrene
1st line – 

intensive supportive care+ surgical debridement ± amputation

Aggressive and thorough surgical debridement is mandatory to improve survival, preserve limbs, and prevent complications.[1][6][23] In patients with extremity involvement, fasciotomy could be necessary to treat compartment syndrome, and it should be done immediately after the diagnosis is made. Daily debridement is necessary, and it is extremely important to remove all necrotic and infected tissue. It is also extremely important to consider amputation of the extremity when necessary, as this could be life-saving.

Intensive haemodynamic support with intravenous infusion is also an important aspect of surgical management.

Plus – intravenous antibiotics

Back
ACUTE
|
gas gangrene
Plus – 

intravenous antibiotics

Treatment recommended for ALL patients in selected patient group

Currently, a combination of penicillin and clindamycin is widely used.[17] Protein synthesis inhibitors (e.g., clindamycin, chloramphenicol, rifampicin, tetracycline) are effective because they inhibit the synthesis of clostridial exotoxins and lessen the local and systemic toxic effects of these proteins.[61]

For patients allergic to penicillin, a combination of clindamycin and metronidazole is a good choice.

Primary options

benzylpenicillin sodium: 2.4 to 4.8 g/day intravenously given in divided doses every 4-6 hours

and

clindamycin: 600-900 mg intravenously every 8 hours

Secondary options

clindamycin: 600-900 mg intravenously every 8 hours

and

metronidazole: 30 mg/kg/day intravenously given in divided doses every 6 hours

ischaemic gangrene

1st line – intravenous heparin

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ACUTE
|
ischaemic gangrene
1st line – 

intravenous heparin

Unless contraindicated, all patients should immediately receive an intravenous heparin bolus, followed by a continuous heparin infusion.[62][63] After the initiation of heparin, treatment then varies depending upon the viability of the limb.

Primary options

heparin: 80 units/kg intravenous bolus, followed by 18 units/kg/hour infusion

Plus – surgical revascularisation ± amputation

Back
ACUTE
|
ischaemic gangrene
|
with threatened or non-viable extremity: life expectancy >2 years
Plus – 

surgical revascularisation ± amputation

Treatment recommended for ALL patients in selected patient group

Patients with a threatened extremity should undergo emergency surgical revascularisation after heparin anticoagulation. The majority of these patients will have had an embolic event, and irreversible changes can occur within as little as 4 to 6 hours of profound ischaemia. While pharmacological thrombolysis may successfully dissolve an embolus, the time required is usually too long to allow this to be an acceptable alternative to surgery.[63]

Patients with a non-viable extremity should undergo prompt amputation. The level of amputation is determined by clinical findings and by the viability of tissues at the time of surgery. Every effort should be made to preserve as many joints as possible, in order to decrease the work of ambulating with a prosthesis and to improve the chances for successful rehabilitation.[46] Revascularisation of the non-viable extremity may be required to allow healing of the amputation or to permit amputation at a lower level.

Plus – percutaneous transluminal angioplasty (PTA) ± amputation

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ACUTE
|
ischaemic gangrene
|
with threatened or non-viable extremity: life expectancy ≤2 years
Plus – 

percutaneous transluminal angioplasty (PTA) ± amputation

Treatment recommended for ALL patients in selected patient group

In the bypass versus angioplasty in severe ischaemia of the leg (BASIL) trial, 450 patients with severe limb ischaemia due to infra-inguinal arterial disease were randomly assigned to PTA or bypass surgery.[65] At 30 days, there was no difference in mortality between the groups, but surgery was associated with a significantly higher morbidity (57% vs. 41%). On intention-to-treat analysis, there was no difference in the primary end point (survival without amputation) at 1 year and 3 years, and surgery was associated with a significantly lower rate of reintervention (18% vs. 26%).

Based on these findings, the authors recommend that PTA should be offered first to patients with significant comorbidities who are not expected to live more than 2 years.

For patients expected to live longer than 2 years, the benefits of bypass surgery could outweigh the short-term increase in morbidity.

Plus – thrombolytic therapy

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ACUTE
|
ischaemic gangrene
|
with viable extremity
Plus – 

thrombolytic therapy

Treatment recommended for ALL patients in selected patient group

The absence of rest pain, sensory loss, and muscle weakness helps differentiate a viable limb from a threatened limb.[67] In highly selected patients, catheter-based intra-arterial thrombolytic therapy may be an alternative to surgery or percutaneous intervention in the management of critical limb ischaemia. The main indication is acute limb ischaemia of less than 14 days' duration in patients with a viable extremity and only limited gangrenous change.[46]

Plus – thrombolytic therapy

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ACUTE
|
ischaemic gangrene
|
with phlegmasia cerulea dolens
Plus – 

thrombolytic therapy

Treatment recommended for ALL patients in selected patient group

Phlegmasia cerulea dolens, a rare condition in which there is total or near-total obstruction of venous drainage from a limb, may be treated by intravenous thrombolytic therapy to help prevent the onset and progression of venous gangrene.[66]

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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

Use of this content is subject to our disclaimer