Hospital-acquired sepsis or septic shock in adults at risk of infection with multidrug-resistant gram-negative bacteria

For adults 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, 2024Dulhunty, 2024:

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

patients without suspected neurological infection or septic shock and not requiring intensive care support: 1 g 8-hourly

patients with suspected neurological infection, but without septic shock and not requiring intensive care support: 2 g 8-hourly; administer the dose over 3 hours1

patients with septic shock or requiring intensive care support: 2 g administered as a loading dose over 30 minutes. After 4 hours, administer 2 g 8-hourly, as consecutive 8-hour infusions23

PLUS

vancomycin 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 for critically ill adults. vancomycin vancomycin vancomycin

For adults in whom toxic shock syndrome is suspected4, add to the above regimen:

clindamycin 600 mg intravenously, 8-hourly for a minimum of 72 hours and until organ function has significantly improved5 clindamycin clindamycin clindamycin

PLUS

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 adults 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 bacterium 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 The modified dosage of meropenem is recommended for patients with suspected neurological infection to ensure adequate drug exposure. Once neurological infection has been excluded, consider switching to the standard dosage.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 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
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 administering the dose over 3 hours or, if neurological infection has been excluded, consider switching to the standard dosage.Return
4 In adults, signs of toxic shock syndrome include hypotension, kidney impairment, coagulopathy, hyperbilirubinaemia, adult respiratory distress syndrome, generalised rash or soft tissue necrosis. For more information, see Streptococcal toxic shock syndrome.Return
5 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