Penicillin hypersensitivity regimens for sepsis or septic shock from a biliary or gastrointestinal tract source other than acalculous cholecystitis

For empirical therapy of sepsis or septic shock from a biliary or gastrointestinal tract source in adults and children who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin and do not have acalculous cholecystitis¹, as a 2-drug regimen, use:

1ceftriaxone 2 g (child 1 month or older: 50 mg/kg up to 2 g) intravenously, daily. For patients with septic shock or requiring intensive care support, use 1 g (child 1 month or older: 50 mg/kg up to 1 g) intravenously, 12-hourly² ceftriaxone ceftriaxone ceftriaxone

1cefotaxime 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly. For patients with septic shock or requiring intensive care support, use 2 g (child 1 month or older: 50 mg/kg up to 2 g) intravenously, 6-hourly³. For dosage adjustment in adults with kidney impairment, see cefotaxime dosage adjustment cefotaxime cefotaxime cefotaxime

PLUS with either of the above drugs

metronidazole 500 mg (child: 12.5 mg/kg up to 500 mg) intravenously, 12-hourly. metronidazole metronidazole metronidazole

For patients who have had a severe immediate⁴ hypersensitivity reaction to a penicillin, the regimens above can be considered if a beta-lactam antibiotic is strongly preferred (for considerations, see Severe immediate hypersensitivity: Implications of cross-reactivity between penicillins and cephalosporins).

For patients who have had a severe immediate⁴ hypersensitivity reaction to a penicillin in whom the regimens above are not used, or for patients who have had a severe delayed⁵ hypersensitivity reaction to a penicillin, as a 2-drug regimen, use:

1gentamicin intravenously; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing gentamicin gentamicin gentamicin

adult: see Gentamicin initial dose calculator for adults for initial dose

child younger than 18 years: 7 mg/kg up to 560 mg for initial dose⁶ ⁷

1tobramycin intravenously; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing tobramycin tobramycin tobramycin

adult: see Tobramycin initial dose calculator for adults for initial dose

child younger than 18 years: 7 mg/kg up to 560 mg for initial dose⁶ ⁷

PLUS with either of the above drugs

clindamycin 600 mg (child: 15 mg/kg up to 600 mg) intravenously, 8-hourly⁸. clindamycin clindamycin clindamycin

If the clindamycin-containing regimen is used and prompt source control is unlikely to occur (eg within 24 hours), consider adding metronidazole because there is increasing resistance to clindamycin in gram-negative anaerobes (especially Bacteroides species); add:

metronidazole 500 mg (child: 12.5 mg/kg up to 500 mg) intravenously, 12-hourly.

If the patient is improving, source control has been achieved, sepsis is resolving, and culture and susceptibility results are not yet available, consider switching to empirical therapy for the source infection; see:

¹ These regimens are not appropriate for patients with acalculous cholecystitis because they do not adequately treat Pseudomonas aeruginosa, a potential pathogen in these infections.Return

² 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 or require intensive care support, a modified dosage of ceftriaxone is recommended. Once the critical illness has resolved, consider switching to the standard dosage.Return

³ 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 or require intensive care support, a modified dosage of cefotaxime is recommended. Once the critical illness has resolved, consider switching to the standard dosage.Return

⁴ Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return

⁵ 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

⁶ For children with obesity, use adjusted body weight to calculate the dose.Return

⁷ The maximum dose does not apply to children with septic shock or requiring intensive care support.Return

⁸ 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