Empirical therapy for septic shock from a urinary tract source in adults

See Approach to managing sepsis and septic shock from a urinary tract source in adults for a discussion of antibiotic choice.

For empirical therapy for septic shock from a urinary tract source in adults, useWorld Health Organization (WHO), 2022:

ceftriaxone 1 g intravenously, 12-hourly ceftriaxone ceftriaxone ceftriaxone

PLUS EITHER

1gentamicin intravenously; see Gentamicin initial dose calculator for adults for initial dose. See Principles of aminoglycoside use for prescribing considerations and subsequent dosing gentamicin gentamicin gentamicin

OR

1tobramycin intravenously; see Tobramycin initial dose calculator for adults for initial dose. See Principles of aminoglycoside use for prescribing considerations and subsequent dosing. tobramycin tobramycin tobramycin

The choice of aminoglycoside should be informed by susceptibilities of expected pathogens in the local antibiogram. Amikacin is more resistant to bacterial enzymatic inactivation than gentamicin or tobramycin, so may be preferred in areas where extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (eg Escherichia Coli) and carbapenemase-producing Enterobacterales (CPEs) are more prevalent. For amikacin dosing, see Amikacin initial dose calculator for adults.

It is widely accepted that gentamicin can be safely used to treat serious infections in pregnancy (eg sepsis or septic shock), despite its category D classification by the Australian Therapeutic Goods AdministrationChean, 2017Glaser, 2015The Royal Women's Hospital, 2023. There are fewer data on the use of tobramycin and amikacin in pregnancy. For more information, see Aminoglycoside use in pregnant people.

For adults who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use the regimen above.

For adults who have had a severe (immediate or delayed)1 hypersensitivity reaction to a penicillin, use gentamicin, tobramycin or amikacin (as above) and seek expert advice.

For adults who are at risk of infection with multidrug-resistant gram-negative bacteria or have contraindications or precautions that preclude aminoglycoside use, while awaiting results of susceptibility testing and expert advice, replace the empirical regimens above withNelson, 2024:

meropenem 1 g intravenously, administered as a loading dose over 30 minutes. After 4 hours, administer 1 g 8-hourly, as consecutive 8-hour infusions2. For dosage adjustment in adults with kidney impairment, see meropenem dosage adjustment. meropenem meropenem meropenem

Empirical antibiotic regimens are intended for initial therapy only (up to 48 hours). Modify therapy as soon as additional information is available (eg results of Gram stain, culture and susceptibility testing of urine or blood samples). Evaluate appropriateness of antibiotic therapy daily, with consideration given to the patient’s clinical status and the principles of antimicrobial stewardship.

Pharmacokinetics may be altered in patients who are critically ill (eg because of enhanced kidney clearance or changes in volume of distribution). To ensure adequate drug exposure in patients who have septic shock, modified dosages of ceftriaxone and meropenem are recommended above. Once the critical illness has resolved, consider switching to the standard dosage – see the regimens for:

1 Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse. Severe delayed hypersensitivity reactions include cutaneous adverse drug reactions (eg drug rash with eosinophilia and systemic symptoms [DRESS], Stevens–Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], severe blistering or desquamative rash), and significant internal organ involvement (eg acute interstitial nephritis).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 (1 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