Mediastinitis following oesophageal rupture in patients with sepsis or septic shock, or a high risk of gram-negative bacteria or Candida species

To determine whether a patient with mediastinitis following oesophageal rupture is at high risk of gram-negative bacteria or Candida species, see Approach to managing mediastinitis following oesophageal rupture.

For patients with mediastinitis following oesophageal rupture who have sepsis or septic shock, start antibiotic therapy within 1 hour of presentation to medical care or, for ward-based patients, development of sepsis or septic shock. Antibiotics should be administered immediately after blood samples are taken for culture. For nonantibiotic management of sepsis or septic shock, see Resuscitation of patients with sepsis or septic shock.

For patients at risk of invasive candidal infection, consider adding empirical antifungal therapy to the antibacterial regimens belowKeighley, 2021 Pastene, 2020 – see Candidaemia (including Candida and related species sepsis).

For mediastinitis following oesophageal rupture in adults and children 2 months or older with sepsis or septic shock, or a high risk of gram-negative bacteria or Candida species, use the results of culture and susceptibility testing to guide initial therapy. If microbiological results are not available, useAbdul-Aziz, 2024 Dulhunty, 2024:

piperacillin+tazobactam intravenously. For dosage adjustment in adults with kidney impairment, see piperacillin+tazobactam dosage adjustment. See below for modification and duration of therapy piperacillin + tazobactam piperacillin+tazobactam piperacillin+tazobactam

patients without septic shock and not requiring intensive care support: 4+0.5 g (child: 100+12.5 mg/kg up to 4+0.5 g) 6-hourly

patients with septic shock or requiring intensive care support: 4+0.5 g (child: 100+12.5 mg/kg up to 4+0.5 g) administered as a loading dose over 30 minutes. After 3 hours, start a continuous infusion of 16+2 g (child: 400+50 mg/kg up to 16+2 g) administered over 24 hours¹ ².

For patients who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use:

cefepime 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly. For dosage adjustment in adults with kidney impairment, see cefepime dosage adjustment. See below for modification and duration of therapy cefepime cefepime cefepime

PLUS

metronidazole 500 mg (child: 12.5 mg/kg up to 500 mg) intravenously, 12-hourly. See below for modification and duration of therapy. metronidazole metronidazole metronidazole

For patients who have had severe immediate³ hypersensitivity reaction to a penicillin, cefepime plus metronidazole (at the dosages 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 immediate³ hypersensitivity reaction to a penicillin in whom cefepime is not used, or for patients who have had a severe delayed⁴ hypersensitivity reaction to a penicillin, meropenem may be suitable⁵. UseAbdul-Aziz, 2024 Dulhunty, 2024:

meropenem intravenously. For dosage adjustment in adults with kidney impairment, see meropenem dosage adjustment. See below for modification and duration of therapy meropenem meropenem meropenem

patients without septic shock and not requiring intensive care support: 1 g (child: 20 mg/kg up to 1 g) 8-hourly⁶

patients with septic shock or requiring intensive care support: 1 g (child: 20 mg/kg up to 1 g) administered as a loading dose over 30 minutes. After 4 hours, administer 1 g (child: 20 mg/kg up to 1 g) 8-hourly, as consecutive 8-hour infusions⁶ ⁷ ⁸.

Modification and duration of therapy: Oesophageal rupture following planned endoscopy is usually detected immediately or shortly after the injuryRyom, 2011. Unlike patients with spontaneous oesophageal rupture caused by severe vomiting (eg Boerhaave syndrome), patients with oesophageal rupture following endoscopy usually have minimal pleural and mediastinal contamination because they were fasting at the time of injuryRyom, 2011. If mediastinitis, and mediastinal or pleural contamination, are subsequently excluded, prolonged broad-spectrum intravenous antimicrobial therapy may not be required. Review the need for ongoing antibiotic therapy at 48 to 72 hours, then daily if therapy continues.

Seek expert advice for ongoing management and duration of therapy. For severe mediastinitis (eg life-threatening or complicated infection), treatment for 4 to 6 weeks (intravenous + oral) may be requiredMcMullan, 2016.

¹ For patients with septic shock or requiring intensive care support, administering the total daily dose of piperacillin+tazobactam over 24 hours 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 standard dose (4+0.5 g [child: 100+12.5 mg/kg up to 4+0.5 g] intravenously, 6-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: penicillins.Return

² The modified dosage of piperacillin+tazobactam 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 Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return

⁴ 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

⁵ In patients with penicillin hypersensitivity, the rate of immune-mediated cross-reactivity with carbapenems is approximately 1%; therefore, meropenem can be considered in supervised settings. However, in patients with a history of a severe cutaneous adverse reaction (eg drug rash with eosinophilia and systemic symptoms [DRESS], Stevens–Johnson syndrome/toxic epidermal necrolysis [SJS/TEN]), consider meropenem only in a critical situation when there are limited treatment options.Return

⁶ 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 for except in children with central nervous system infection.Return

⁷ 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 [child: 20 mg/kg up to 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

⁸ 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