Hospital-acquired sepsis or septic shock in children 2 months or older at risk of infection with multidrug-resistant gram-negative bacteria

For children 2 months or older with hospital-acquired sepsis or septic shock of unknown source who are at risk of infection with multidrug-resistant gram-negative bacteria, while awaiting results of susceptibility testing and expert advice, consider empirical therapy withAbdul-Aziz, 2024 Dulhunty, 2024:

meropenem intravenously¹ meropenem

child without septic shock and not requiring intensive care support: 40 mg/kg up to 2 g, 8-hourly; administer the dose over 3 hours²

child with septic shock or requiring intensive care support: 40 mg/kg up to 2 g administered as a loading dose over 30 minutes. After 4 hours, administer 40 mg/kg up to 2 g, 8-hourly, as consecutive 8-hour infusions³ ⁴

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vancomycin intravenously; for initial dosing, see Intermittent vancomycin dosing for young infants and children. vancomycin

Prioritise administration of meropenem, because vancomycin requires slow infusion.

For children 2 months or older in whom toxic shock syndrome is suspected⁵, add to the above regimen:

clindamycin 15 mg/kg up to 600 mg intravenously, 8-hourly for a minimum of 72 hours and until organ function has significantly improved⁶ clindamycin

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

For children at risk of invasive Candida infection, consider the addition of an empirical antifungal.

If infection with carbapenem-resistant gram-negative bacteria (including carbapenemase-producing Enterobacterales) is suspected, the meropenem plus vancomycin regimen above may be given while awaiting advice from a clinical microbiologist or infectious diseases physician. Alternatively, if available, follow local guidelines.

Note: Management of infection with carbapenem-resistant gram-negative bacteria is challenging and beyond the scope of these guidelines – seek expert advice.

See Managing suspected infection with multidrug-resistant gram-negative bacteria for advice on obtaining a thorough history in patients with suspected multidrug-resistant gram-negative infection, practical information on common acquired resistance mechanisms, and antimicrobials that may remain effective against multidrug-resistant gram-negative bacteria. However, this advice is not a substitute for expert advice – always consult a clinical microbiologist or infectious diseases physician.

This empirical regimen is intended for initial therapy only (up to 48 hours). Modify therapy as soon as additional information is available (eg source of infection, results of Gram stain, culture and susceptibility testing). Evaluate the appropriateness of antimicrobial therapy daily, with consideration given to the patient’s clinical status and the principles of antimicrobial stewardship.

¹ 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

² This higher dose of meropenem (40 mg/kg up to 2 g intravenously, 8-hourly) is recommended to treat potential central nervous system infection, which is more common in children. If central nervous system infection has been excluded and the child is not critically ill (ie does not have septic shock nor require intensive care support), 20 mg/kg up to 1 g intravenously, 8-hourly may be used.Return

³ 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 (40 mg/kg up to 2 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

⁴ 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 administering the dose over 3 hours or, if neurological infection has been excluded, consider switching to the standard dosage (20 mg/kg up to 1 g intravenously, 8-hourly).Return

⁵ In children, signs of toxic shock syndrome include fever, hypotension, rash and evidence of organ dysfunction. For more information, see Streptococcal toxic shock syndrome.Return

⁶ 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