Febrile neutropenia: empirical therapy with activity against multidrug-resistant Gram-negative bacteria

The following empirical regimens are intended for initial therapy only. Modify therapy as soon as additional information or expert advice is available. Evaluate appropriateness of antimicrobial therapy daily, with consideration given to the patient’s clinical status and the principles of antimicrobial stewardship.

A broader-spectrum regimen is appropriate for patients colonised, or recently infected, with a multidrug-resistant Gram-negative bacterium (particularly if the patient has sepsis or septic shock, or requires intensive care support), but is not indicated on the basis of other risk factors for resistant infection.

Note: Broader-spectrum therapy is not indicated for patients with risk factors for infection with a multidrug-resistant Gram-negative bacterium, except if known to be colonised or recently infected with a resistant bacterium.

If broader-spectrum therapy is indicated, for isolates susceptible to carbapenems, use:

meropenem intravenously. For dosage adjustment in adults with kidney impairment, see meropenem dosage adjustment febrile neutropenia, MDR Gram-negative activity meropenem

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

patients with septic shock or requiring intensive care support: 2 g (child: 40 mg/kg up to 2 g) administered as a loading dose over 30 minutes. After 4 hours, administer 2 g (child: 40 mg/kg up to 2 g) 8-hourly, as consecutive 8-hour infusions² ³.

For isolates not susceptible to carbapenems, seek expert advice.

Add vancomycin to meropenem if the patient has sepsis or septic shock, or requires intensive care support.

Consider adding vancomycin to meropenem if the patient has:

an increased risk of methicillin-resistant Staphylococcus aureus (MRSA) infection (see Risk factors for infection with methicillin-resistant Staphylococcus aureus)
an intravascular catheter-related infection in a unit with a significant incidence of MRSA infection.

The role of empirical vancomycin for patients with severe mucositis is uncertain and should be considered on an individual basis—seek expert advice.

If vancomycin is indicated, use:

vancomycin intravenously; see Vancomycin dosing in adults or Intermittent vancomycin dosing for young infants and children for initial dosing. Loading doses are recommended for critically ill adults. febrile neutropenia, MDR Gram-negative activity vancomycin

Early antifungal therapy may be required for patients suspected to have fungal infection, including unstable patients at high risk of fungal infection.

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 infection or critical illness (ie those with septic shock or requiring intensive care support).Return

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 (2 g [child: 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

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