Pseudomonas aeruginosa sepsis or septic shock

Australian Commission on Safety and Quality in Health Care (ACSQHC), 2023

For Pseudomonas aeruginosa sepsis or septic shock, a beta lactam is used in combination with an aminoglycoside or ciprofloxacin. As a 2-drug regimen, useAbdul-Aziz, 2024 Dulhunty, 2024:

1ceftazidime 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly¹. For dosage adjustment in adults with kidney impairment, see ceftazidime dosage adjustment. See advice on modification and duration of therapy ceftazidime ceftazidime ceftazidime

OR

2cefepime 2g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly². For dosage adjustment in adults with kidney impairment, see cefepime dosage adjustment. See advice on modification and duration of therapy cefepime cefepime cefepime

OR

2piperacillin+tazobactam intravenously. For dosage adjustment in adults with kidney impairment, see piperacillin+tazobactam dosage adjustment. See advice on 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-hourly³

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 hours⁴ ⁵

PLUS with one of the above drugs, one of the following

1tobramycin intravenously; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing. See advice on modification and duration of therapy 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

OR

2gentamicin intravenously; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing. See advice on modification and duration of therapy 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

OR

3ciprofloxacin 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 modification and duration of therapy. ciprofloxacin ciprofloxacin ciprofloxacin

An aminoglycoside is preferred to ciprofloxacin for combination empirical therapy because current epidemiology suggests susceptibility to aminoglycosides is more likely. Even in patients with kidney failure, a single dose of an aminoglycoside may be considered in rapidly deteriorating, critically ill patients. The choice of aminoglycoside may be influenced by several factors, including:

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

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

For patients who have had a nonsevere (immediate or delayed) or a severe immediate⁹ hypersensitivity reaction to a penicillin, use a cefepime- or ceftazidime-based regimen (as above).

For patients who have had a severe delayed¹⁰ hypersensitivity reaction to a penicillin, as a 2-drug regimen, useAbdul-Aziz, 2024 Dulhunty, 2024:

meropenem intravenously¹¹. For dosage adjustment in adults with kidney impairment, see meropenem dosage adjustment. See advice on 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-hourly¹² ¹³

patients with septic shock or requiring intensive care support: 2 g (child: 40 mg/kg up to 2 g) administered as a loading dose over 30 minutes. After 4 hours, administer 2 g (child: 40 mg/kg up to 2 g) 8-hourly, as consecutive 8-hour infusions ¹⁴ ¹⁵

PLUS one of the following

1tobramycin intravenously; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing. See advice on modification and duration of therapy 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

OR

2gentamicin intravenously; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing. See advice on modification and duration of therapy 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

OR

3ciprofloxacin 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 modification and duration of therapy. ciprofloxacin ciprofloxacin ciprofloxacin

¹ In patients with septic shock or requiring intensive care support, there is a theoretical benefit from administering the intermittent dose of ceftazidime 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

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 For directed therapy of pseudomonal infections in patients without septic shock and those not requiring intensive care support, administration of piperacillin+tazobactam over 3 hours is preferred to ensure adequate drug exposure. However, when this is not possible (eg the patient is receiving other drugs via the same line), piperacillin+tazobactam may be administered over 30 minutes. For more information, see Practical information on using beta lactams: penicillins.Return

⁴ 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

⁵ 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. If the isolate is not reported to have dose-dependent susceptibility to piperacillin+tazobactam (ie susceptible dose dependent [SDD] or susceptible increased exposure [I or SIE]), it may also be appropriate to switch to the standard dose – seek expert advice.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 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 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 If neurological infection is suspected, a higher dosage of meropenem is required (2 g [child 40 mg/kg up to 2 g] intravenously, 8-hourly; administer the dose over 3 hours).Return

¹³ 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 critical illness (ie those with septic shock or requiring intensive care support).Return

¹⁴ 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 (2 g [child: 40 mg/kg up to 2 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

¹⁵ 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. If the isolate is not reported to have dose-dependent susceptibility to meropenem (ie susceptible dose dependent [SDD] or susceptible increased exposure [I or SIE]), it may also be appropriate to switch to the standard dosage – seek expert advice.Return