Patients with septic shock or requiring intensive care support
The following empirical regimens are intended for initial therapy only. Modify therapy as soon as additional information or expert advice is available. Evaluate appropriateness of antimicrobial therapy daily, with consideration given to the patient’s clinical status and the principles of antimicrobial stewardship.
For patients with septic shock or requiring intensive care support (including patients with risk factors for infection with a multidrug-resistant Gram-negative bacterium, except if known to be colonised or recently infected with a resistant bacterium), the combination of an antipseudomonal beta lactam, gentamicin, and vancomycin is recommended. Use:
gentamicin intravenously; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing febrile neutropenia, no MDR Gram-negative activity, septic shock 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 dose1
PLUS
vancomycin intravenously febrile neutropenia, no MDR Gram-negative activity, septic shock 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: see Intermittent vancomycin dosing for young infants and children for initial vancomycin dose
PLUS any of the following
1 piperacillin+tazobactam 4+0.5 g (child: 100+12.5 mg/kg up to 4+0.5 g) intravenously, as a loading dose administered over 30 minutes. After 3 hours, start a continuous infusion of 16+2 g (child 400+50 mg up to 16+2 g) administered over 24 hours2. For dosage adjustment in adults with kidney impairment, see piperacillin+tazobactam dosage adjustment febrile neutropenia, no MDR Gram-negative activity, septic shock piperacillin + tazobactam
OR
1 cefepime 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly 3 4. For dosage adjustment in adults with kidney impairment, see cefepime dosage adjustment febrile neutropenia, no MDR Gram-negative activity, septic shock cefepime
OR
1 ceftazidime 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly456. For dosage adjustment in adults with kidney impairment, see ceftazidime dosage adjustment. febrile neutropenia, no MDR Gram-negative activity, septic shock ceftazidime
Prioritise administration of piperacillin+tazobactam, cefepime or ceftazidime, and gentamicin, because vancomycin requires slow infusion.
Early antifungal therapy is required for patients suspected to have fungal infection. The choice of treatment depends on the prophylactic antifungal regimen used—seek expert advice.
For patients who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use a cefepime- or ceftazidime-based regimen, as above.
For patients who have had a severe immediate hypersensitivity reaction to a penicillin7, a cefepime- or ceftazidime-based regimen (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 immediate hypersensitivity reaction to a penicillin in whom a cefepime- or ceftazidime-based regimen is not used7, or for patients who have had a severe delayed hypersensitivity reaction to a penicillin8, seek expert advice.
If the results of susceptibility testing are not available by 72 hours and empirical intravenous therapy is still required, seek expert advice; empirical gentamicin dosing should not continue beyond 48 hours, and vancomycin may not be required if the patient is clinically improving.