Empirical therapy for suspected pseudomonal high-severity CAP in children 2 months or older

Pseudomonas aeruginosa is a rare cause of CAP in children 2 months or older. Identification of P. aeruginosa in sputum may represent colonisation rather than pneumonia. For treatment of P aeruginosa exacerbations of bronchiectasis, see Antibiotic management of bronchiectasis in children or, for cystic fibrosis, see Airway infection and antibiotic therapy in cystic fibrosis.

Note: P. aeruginosa is a rare cause of CAP; identification of P. aeruginosa in sputum may represent colonisation rather than pneumonia.

Consider empirical antipseudomonal therapy for high-severity CAP in children 2 months or older with known colonisation of sputum with P. aeruginosa (eg some children with a tracheostomy, bronchiectasis, tube feeding) and one of the following:

  • gram-negative bacilli predominant on Gram stain or identified by culture of sputum1 or blood (pending identification)
  • life-threatening pneumonia.

Do not use previous susceptibility results to guide current antipseudomonal therapy unless the sample was taken recently (eg in the last month).

If empirical antipseudomonal therapy is indicated for high-severity CAP in children 2 months or older, replace the empirical therapy regimen with:

1cefepime 50 mg/kg up to 2 g intravenously, 8-hourly2 cefepime

OR

1piperacillin+tazobactam intravenously piperacillin + tazobactam

child without septic shock: 100+12.5 mg/kg up to 4+0.5 g, 6-hourly3

child with septic shock: 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 400+50 mg/kg up to 16+2 g, administered over 24 hours45

PLUS with either of the above regimens for children with life-threatening pneumonia

1tobramycin 7 mg/kg up to 560 mg6 intravenously for initial dose7; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing tobramycin

OR

2gentamicin 7 mg/kg up to 560 mg8 intravenously for initial dose7; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing. gentamicin

The choice of aminoglycoside may be influenced by several factors, including:

  • the spectrum of activity
  • the availability of aminoglycoside therapeutic drug monitoring
  • whether the laboratory reports aminoglycoside susceptibility
  • drug cost.

There are limited clinical data to support tobramycin over gentamicin; however, the minimum inhibitory concentration (MIC) for tobramycin is slightly lower than gentamicin in vitro (particularly for P. aeruginosa) and has a greater likelihood of target attainment.

For children 2 months or older with suspected pseudomonal high-severity CAP who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use the cefepime-based regimen above.

For children 2 months or older with suspected pseudomonal high-severity CAP who have had a severe immediate9 hypersensitivity reaction to a penicillin, the cefepime-based regimen 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 children 2 months or older with suspected pseudomonal high-severity CAP who have had a severe immediate9 hypersensitivity reaction to a penicillin in whom cefepime is not used, or for patients who have had a severe delayed10 hypersensitivity reaction to a penicillin, replace the empirical therapy regimen with:

meropenem intravenously11 meropenem

child without septic shock: 40 mg/kg up to 2 g, 8-hourly; administer the dose over 3 hours

child with septic shock: 40 mg/kg up to 2 g, administered as a loading dose over 30 minutes. After 4 hours, administer 40 mg/kg up to 2 g, 8-hourly, as consecutive 8-hour infusions1213

PLUS with either of the above regimens for children with life-threatening pneumonia

1tobramycin 7 mg/kg up to 560 mg6 intravenously for initial dose7; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing tobramycin

OR

2gentamicin 7 mg/kg up to 560 mg8 intravenously for initial dose7; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing. gentamicin

If P. aeruginosa is confirmed, modify therapy based on the results of culture and susceptibility testing if possible – see Pseudomonas aeruginosa pneumonia. If P. aeruginosa is not identified, switch to a narrower-spectrum empirical regimen or, if another pathogen is identified, see Directed therapy for pneumonia.

1 Gram stain of poor-quality sputum samples can give misleading results. Use a good-quality sample (presence of polymorphs but few or no squamous epithelial cells on microscopy), collected before starting antibiotics, to adjust antibiotic therapy – the pathogen should be predominant in the Gram stain as well as the culture.Return
2 In patients with septic shock or requiring intensive care support, there is a theoretical benefit from administering the intermittent dose of cefepime over 3 to 4 hours, or administering the daily dose over 24 hours. However, at the time of writing, there are inadequate data to recommend administration over 3 hours or longer for patients with septic shock or requiring intensive care support.Return
3 Administration of piperacillin+tazobactam over 3 hours may be preferred to ensure adequate drug exposure for Pseudomonas aeruginosa. For more information, see Practical information on using beta lactams: penicillins.Return
4 For children with septic shock, 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 child is receiving other drugs via the same line), administer the standard dose (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
5 The modified dosage of piperacillin+tazobactam for children with septic shock 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
6 The maximum dose of tobramycin does not apply to children with septic shock or requiring intensive care support.Return
7 For children with obesity, use adjusted body weight to calculate the dose.Return
8 The maximum dose of gentamicin does not apply to children with septic shock or requiring intensive care support.Return
9 Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return
10 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
11 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
12 For children with septic shock, 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 child is receiving other drugs via the same line), administer the dose (40 mg/kg up to 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
13 The modified dosage of meropenem for children with septic shock 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. If infection with Pseudomonas aeruginosa has been excluded, consider switching to the standard dosage.Return