Empirical therapy for necrotising skin and soft tissue infection not associated with water exposure

For necrotising skin and soft tissue infections, empirical antibiotic therapy should be used in combination with surgical debridement. In adults and children with necrotising skin and soft tissue infection not associated with water exposure, as a 3-drug regimen, useAbdul-Aziz 2024Dulhunty 2024:

meropenem intravenously. For dosage adjustment in adults with kidney impairment, see meropenem dosage adjustment. See advice on modification and duration of therapy meropenem meropenem meropenem

patients without septic shock and not requiring intensive care support: 1 g (child: 20 mg/kg up to 1 g) 8-hourly1

patients with septic shock or requiring intensive care support: 1 g (child: 20 mg/kg up to 1 g) administered as a loading dose over 30 minutes. After 4 hours, administer 1 g (child: 20 mg/kg up to 1 g) 8-hourly, as consecutive 8-hour infusions123

PLUS

vancomycin intravenously; see advice on modification and duration of therapy vancomycin vancomycinvancomycin

adult: 25 mg/kg (actual body weight) rounded up to nearest 125 mg, up to 3 g intravenously, as a loading dose. See Calculated vancomycin loading dosage in critically ill adults for calculated weight-based loading doses. Subsequent doses are dependent on weight and kidney function; see Intermittent vancomycin dosing in critically ill adults

child: for initial dosing, see Intermittent vancomycin dosing in young infants and children

PLUS

clindamycin 600 mg (child: 15 mg/kg up to 600 mg) intravenously, 8-hourly4. See advice on modification and duration of therapy.clindamycin clindamycin clindamycin

If meropenem is not immediately available or if there is a low suspicion of multidrug-resistant gram-negative infection, piperacillin+tazobactam may be a suitable alternative to meropenem. Replace meropenem in the above regimen withAbdul-Aziz 2024Dulhunty 2024:

piperacillin+tazobactam intravenously. For dosage adjustment in adults with kidney impairment, see piperacillin+tazobactam dosage adjustment. See advice on modification and duration of therapy piperacillin + tazobactam piperacillin+tazobactam piperacillin+tazobactam

patients without septic shock and not requiring intensive care support: 4+0.5 g (child: 100+12.5 mg/kg up to 4+0.5 g) 6-hourly

patients with septic shock or requiring intensive care support: 4+0.5 g (child: 100+12.5 mg/kg up to 4+0.5 g) administered as a loading dose over 30 minutes. After 3 hours, start a continuous infusion of 16+2 g (child: 400+50 mg/kg up to 16+2 g) administered over 24 hours56.

For patients who report hypersensitivity to penicillins (for advice on assessing and managing hypersensitivity, see Approach to assessment and management of patients reporting hypersensitivity to penicillins in whom a beta-lactam antibiotic is the preferred drug), the meropenem-containing regimen7 may be suitable.

Note: The Antibiotic Expert Group recommend that intravenous immunoglobulin be used if Streptococcus pyogenes necrotising fasciitis is suspected.

The Antibiotic Expert Group recommend that intravenous immunoglobulin be used if Streptococcus pyogenes necrotising fasciitis is suspected (typically infection involving a limb and associated with nonpenetrating trauma or an injury that breaks the skin). Add to either of the above regimensKadri 2017Linner 2014:

intravenous immunoglobulin (IVIg) (adult and child) 2 g/kg intravenously, as a single dose as soon as possible but not later than 72 hours after symptom onset. It is reasonable to give the dose in divided doses if it is not possible to give a single dose. intravenous immunoglobulin (IVIg) intravenous immunoglobulin (IVIg)

Clindamycin is recommended for empirical therapy of necrotising skin and soft tissue infection because of a theoretical reduction in bacterial toxin production; however, clinical evidence is limited.

1 Some centres use a meropenem dosage of 40 mg/kg up to 2 g intravenously, 8-hourly for children who are very unwell; however, no data are available to support the use of this dosage except in children with central nervous system infectionReturn
2 For patients with septic shock or requiring intensive care support, administering the total daily dose of meropenem over 24 hours (as 3 consecutive 8-hourly infusions) is preferred to ensure adequate drug exposure. If this is not possible (eg the patient is receiving other drugs via the same line), administer the dose (1 g [child: 20 mg/kg up to 1 g] 8-hourly) as an extended infusion over 3 hours. If a 3-hour infusion is not possible, administer over 30 minutes. For more information, see Practical information on using beta lactams: carbapenems.Return
3 The modified dosage of meropenem for patients with septic shock or those requiring intensive care support is recommended to ensure adequate drug exposure, because pharmacokinetics may be altered in patients with critical illness (eg because of enhanced kidney clearance or changes in volume of distribution). Once the critical illness has resolved, consider switching to the standard dosage.Return
4 There are more clinical and microbiological data to support the use of clindamycin than lincomycin. Intravenous lincomycin can be used at the same dosage if clindamycin is unavailable or if a local protocol recommends its use.Return
5 For patients with septic shock or requiring intensive care support, administering the total daily dose of piperacillin+tazobactam over 24 hours is preferred to ensure adequate drug exposure. If this is not possible (eg the patient is receiving other drugs via the same line), administer the standard dose (4+0.5 g [child: 100+12.5 mg/kg up to 4+0.5 g] intravenously, 6-hourly) as an extended infusion over 3 hours. If a 3-hour infusion is not possible, administer over 30 minutes. For more information, see Practical information on using beta lactams: penicillins.Return
6 The modified dosage of piperacillin+tazobactam for patients with septic shock or those requiring intensive care support is recommended to ensure adequate drug exposure, because pharmacokinetics may be altered in patients with critical illness (eg because of enhanced kidney clearance or changes in volume of distribution). Once the critical illness has resolved, consider switching to the standard dosage.Return
7 In patients with penicillin hypersensitivity, the rate of immune-mediated cross-reactivity with carbapenems is approximately 1%; therefore, meropenem can be considered in supervised settings. However, in patients with a history of a severe cutaneous adverse reaction (eg drug rash with eosinophilia and systemic symptoms [DRESS], Stevens–Johnson syndrome/toxic epidermal necrolysis [SJS/TEN]), consider meropenem only in a critical situation when there are limited treatment options.Return