Multidrug-resistant Enterobacterales pneumonia

Australian Commission on Safety and Quality in Health Care (ACSQHC), 2023Kalil, 2016

Multidrug-resistant (MDR) Enterobacterales include extended-spectrum beta-lactamase (ESBL)–producing Enterobacterales, AmpC beta-lactamase–producing Enterobacterales and carbapenemase-producing Enterobacterales.

For management of pneumonia caused by Klebsiella pneumoniae and Escherichia coli isolates that are nonmultidrug-resistant (non-MDR), see Nonmultidrug-resistant Enterobacterales pneumonia.

Note: Consult a clinical microbiologist or infectious diseases physician for management of multidrug-resistant Enterobacterales pneumonia.

Management of pneumonia caused by ESBL-producing Enterobacterales is complex – consult a clinical microbiologist or infectious diseases physician.

For initial therapy in adults with pneumonia caused by ESBL-producing Enterobacterales, while awaiting further advice, use Abdul-Aziz, 2024Dulhunty, 2024:

meropenem intravenously. For dosage adjustment in adults with kidney impairment, see meropenem dosage adjustment meropenem meropenem meropenem

adult without septic shock and not requiring intensive care support: 1 g 8-hourly

adult with septic shock or requiring intensive care support: 1 g administered as a loading dose over 30 minutes. After 4 hours, administer 1 g 8-hourly, as consecutive 8-hour infusions12.

For initial therapy in children with pneumonia caused by ESBL-producing Enterobacterales, while awaiting further advice, useAbdul-Aziz, 2024Dulhunty, 2024:

meropenem intravenouslymeropenem

child without septic shock: 20 mg/kg up to 1 g, 8-hourly3

child with septic shock: 20 mg/kg up to 1 g, administered as a loading dose over 30 minutes. After 4 hours, administer 20 mg/kg up to 1 g, 8-hourly, as consecutive 8-hour infusions345.

If results of susceptibility tests identify E. coli or K. pneumoniae isolates resistant to broad-spectrum cephalosporins but susceptible to piperacillin+tazobactam and meropenem, use meropenem because the risk of mortality is increased in patients treated with piperacillin+tazobactam Harris, 2018.

Some Enterobacterales produce AmpC beta-lactamases, although not all isolates will produce the enzyme in clinically significant amounts. Enterobacterales that cause pneumonia and are at high risk of clinically significant AmpC production are Enterobacter cloacae and Klebsiella aerogenes. Management of pneumonia caused by AmpC beta-lactamase–producing Enterobacterales is complex – consult a clinical microbiologist or infectious diseases physician.

For initial therapy in adults with pneumonia caused by AmpC beta-lactamase–producing Enterobacterales, while awaiting further advice, use:Abdul-Aziz, 2024Dulhunty, 2024

cefepime 2 g intravenously, 8-hourly. For dosage adjustment in adults with kidney impairment, see cefepime dosage adjustment cefepime cefepime cefepime

OR if the patient is critically ill (has septic shock or requires intensive care support)

meropenem 1 g intravenously, administered as a loading dose over 30 minutes. After 4 hours, administer 1 g 8-hourly, as consecutive 8-hour infusions16. For dosage adjustment in adults with kidney impairment, see meropenem dosage adjustment. meropenem meropenem meropenem

For initial therapy in children with pneumonia caused by AmpC beta-lactamase–producing Enterobacterales, while awaiting further advice, use:Abdul-Aziz, 2024Dulhunty, 2024

cefepime 50 mg/kg up to 2 g intravenously, 8-hourlycefepime

OR if the child has septic shock

meropenem 20 mg/kg up to 1 g intravenously, administered as a loading dose over 30 minutes. After 4 hours, administer 20 mg/kg up to 1 g, 8-hourly, as consecutive 8-hour infusions34 7.meropenem

Management of pneumonia due to carbapenemase-producing Enterobacterales is extremely challenging and beyond the scope of this topic. 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.

1 For adults 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 intravenously 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
2 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
3 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.Return
4 For children with septic shock, 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 child is receiving other drugs via the same line), administer the dose (20 mg/kg up to 1 g intravenously, 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
5 The modified dosage of meropenem for children with septic shock 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
6 The modified dosage of meropenem for adults 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 administration over 30 minutes.Return
7 Administering meropenem as 3 consecutive 8-hourly infusions 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 administration over 30 minutes.Return