Patients without septic shock and not 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 without septic shock and not 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), use:

1 piperacillin+tazobactam 4+0.5 g (child: 100+12.5 mg/kg up to 4+0.5 g) intravenously, 6-hourly. For dosage adjustment in adults with kidney impairment, see piperacillin+tazobactam dosage adjustment febrile neutropenia, no MDR Gram-negative activity, not septic shock piperacillin + tazobactam    

OR

1 cefepime 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly1. For dosage adjustment in adults with kidney impairment, see cefepime dosage adjustment febrile neutropenia, no MDR Gram-negative activity, not septic shock cefepime    

OR

1 ceftazidime 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly12. For dosage adjustment in adults with kidney impairment, see ceftazidime dosage adjustment. febrile neutropenia, no MDR Gram-negative activity, not septic shock ceftazidime    

Add vancomycin to the above regimens if the patient has sepsis.

Consider adding vancomycin to the above regimens if the patient has:

The role of empirical vancomycin for patients with severe mucositis is uncertain and should be considered on an individual basis—seek expert advice.

If vancomycin is indicated, use:

vancomycin intravenously; see Intermittent vancomycin dosing in noncritically ill adults or Intermittent vancomycin dosing for young infants and children for initial dosing. febrile neutropenia, no MDR Gram-negative activity, not septic shock vancomycin    

If vancomycin is included in the empirical regimen, review its use after 48 to 72 hours. If culture and susceptibility results are not available by 72 hours and empirical intravenous therapy is still required, it is not necessary to continue treatment with vancomycin empirically provided that the patient is clinically improving.

Early antifungal therapy may be required for patients suspected to have fungal infection, including unstable patients at high risk of fungal infection.

For patients who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use cefepime or ceftazidime, with or without vancomycin, as above.

For patients who have had a severe immediate hypersensitivity reaction to a penicillin3, cefepime or ceftazidime (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 immediate hypersensitivity reaction to a penicillin in whom cefepime or ceftazidime is not used3, or for patients who have had a severe delayed hypersensitivity reaction to a penicillin4, seek expert advice.

1 Compared to piperacillin+tazobactam, ceftazidime and cefepime have inferior activity against anaerobic bacteria. If infection with anaerobic bacteria is suspected (eg patients with enterocolitis), consider using piperacillin+tazobactam instead, or adding metronidazole to ceftazidime or cefepime. Return
2 Compared to piperacillin+tazobactam and cefepime, ceftazidime has inferior activity against Gram-positive bacteria. If infection with a Gram-positive bacterium is suspected (eg patients with mucositis), consider using piperacillin+tazobactam or cefepime instead. 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