Standard regimen for hospital-acquired septic shock in adults

In adults with hospital-acquired septic shock of unknown source, antibiotic choice depends on whether toxic shock is suspected and whether the patient is at risk of invasive Candida infection. If the patient is at risk of invasive Candida infection, consider the addition of an antifungal.

For adults with hospital-acquired septic shock without an apparent source of infection, in the absence of local protocols or advice, as a 2-drug regimen, useAbdul-Aziz, 2024Dulhunty, 2024:

piperacillin+tazobactam 4+0.5 g intravenously, administered as a loading dose over 30 minutes. After 3 hours, start a continuous infusion of 16+2 g administered over 24 hours1. For dosage adjustment in adults with kidney impairment, see piperacillin+tazobactam dosage adjustment

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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 suspected2, add to the above regimen:

clindamycin 600 mg intravenously, 8-hourly for a minimum of 72 hours and until organ function has significantly improved3 clindamycin clindamycin 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.

These empirical regimens are 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.

Cefepime is a reasonable alternative to piperacillin+tazobactam – some centres may prefer to use cefepime for the empirical treatment of hospital-acquired septic shock. For an appropriate cefepime regimen, see Penicillin hypersensitivity regimens for hospital-acquired septic shock in adults.

Systematic reviews suggest that adding an aminoglycoside to the empirical regimen for hospital-acquired sepsis or septic shock is associated with increased toxicity without additional clinical benefit. However, for patients with septic shock, adding an aminoglycoside may be appropriate if there is suspicion of infection with gram-negative organisms resistant to piperacillin+tazobactam. This practice is most useful if local microbiological data show a significant proportion of gram-negative organisms are susceptible to aminoglycosidesDickinson, 2011.

1 Pharmacokinetics may be altered in patients with septic shock (eg because of enhanced kidney clearance or changes in volume of distribution). Administering the total daily dose of piperacillin+tazobactam over 24 hours is preferred in patients with septic shock to ensure adequate drug exposure. If this is not possible (eg the patient is receiving other drugs via the same line), use intermittent dosing of piperacillin+tazobactam 4+0.5 g intravenously, 6-hourly, administered as an extended infusion over 3 hours. If a 3-hour infusion is not possible, administer over 30 minutes. Once septic shock has resolved, consider switching from continuous to intermittent dosing. For more information, see Practical information on using beta lactams: penicillins.Return
2 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
3 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