Empirical therapy for VAP in patients at increased risk of infection with Pseudomonas aeruginosa

Empirical therapy for ventilator-associated pneumonia (VAP) is stratified according to the risk of infection with Pseudomonas aeruginosa (see Approach to managing VAP).

For empirical therapy of VAP in adults at increased risk of infection with P. aeruginosa, 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. See advice on patient review, intravenous to oral switch, duration of therapy and follow-up. piperacillin + tazobactam piperacillin+tazobactam piperacillin+tazobactam

For empirical therapy of VAP in children at increased risk of infection with P. aeruginosa, useAbdul-Aziz, 2024Dulhunty, 2024:

piperacillin+tazobactam intravenously. See advice on patient review, intravenous to oral switch, duration of therapy and follow-up piperacillin + tazobactam

children without septic shock: 100+12.5 mg/kg up to 4+0.5 g, 6-hourly2

children 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 hours34.

When prescribing empirical therapy, consider the need for additional therapy for patients with:

For patients who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use cefepime and consider the need for additional therapy for VAP:

cefepime 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly5. For dosage adjustment in adults with kidney impairment, see cefepime dosage adjustment. See advice on patient review, intravenous to oral switch, duration of therapy and follow-up. cefepime cefepime cefepime

For patients who have had a severe immediate6 hypersensitivity reaction to a penicillin, cefepime (at the dosage 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 immediate6 hypersensitivity reaction to a penicillin in whom cefepime is not used, or for patients who have had a severe delayed7 hypersensitivity reaction to a penicillin, useAbdul-Aziz, 2024Dulhunty, 2024:

1ciprofloxacin 400 mg (child: 10 mg/kg up to 400 mg) intravenously, 8-hourly8. For dosage adjustment in adults with kidney impairment, see ciprofloxacin intravenous dosage adjustment. See advice on patient review, intravenous to oral switch, duration of therapy and follow-up ciprofloxacin ciprofloxacin ciprofloxacin

PLUS

vancomycin intravenously; see advice on patient review, intravenous to oral switch, duration of therapy and follow-up vancomycin vancomycin vancomycin

adult: 25 mg/kg (actual body weight) rounded up to nearest 125 mg, up to 3 g, 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 in critically ill adults

child: for initial dosing, see Intermittent vancomycin dosing in young infants and children

OR as a single drug

1meropenem intravenously9. See advice on patient review, intravenous to oral switch, duration of therapy and follow-up meropenem meropenem meropenem

adult: 2 g administered as a loading dose over 30 minutes. After 4 hours, administer 2 g, 8-hourly, as consecutive 8-hour infusions10. For dosage adjustment in adults with kidney impairment, see meropenem dosage adjustment

child without septic shock: 20 mg/kg up to 1 g, 8-hourly11

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.

Also consider the need for additional therapy for VAP when prescribing the above regimens.

1 Pharmacokinetics may be altered in patients who are critically ill (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 initially for adults with VAP 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 critical illness has resolved, consider switching from continuous to intermittent dosing. For more information, see Practical information on using beta lactams: penicillins.Return
2 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
3 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
4 The modified dosage of piperacillin+tazobactam for patients 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
5 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
6 Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return
7 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
8 Ciprofloxacin is not licensed for use in children on the basis of animal studies that showed an adverse effect on cartilage development with quinolone use; however, clinical trial data suggest that adverse musculoskeletal events are usually mild and short term, similar to those observed in adults. Ciprofloxacin can be used in children when it is the drug of choice.Return
9 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
10 Pharmacokinetics may be altered in patients who are critically ill (eg because of enhanced kidney clearance or changes in volume of distribution). Administering the total daily dose of meropenem over 24 hours is preferred initially for adults with VAP 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 meropenem 2 g intravenously, 8-hourly, administered as an extended infusion over 3 hours. If a 3-hour infusion is not possible, administer over 30 minutes. Once critical illness has resolved, consider switching from continuous to intermittent dosing. For more information, see Practical information on using beta lactams: carbapenems.Return
11 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 except in children with central nervous system infection or septic shock.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 or Acinetobacter baumannii have been excluded, consider switching to the standard dosage.Return