Sepsis

Sepsis is a medical emergency.

See Sepsis in Adults and Immunosuppressed Patients in Hospital HealthPathways.

• Take two blood cultures (more if endocarditis suspected) before initiating empiric antimicrobial therapy as in the relevant guideline below. Also culture for other sources of infection, if possible, but do not delay initiating antimicrobial therapy in a deteriorating patient.

  Blood cultures for suspected endocarditis

  If endocarditis is suspected:

  • Before starting antibiotics, take at least 3 sets of cultures (3 venepunctures, 6 bottles) by venepuncture.
  • If antibiotic use within the last 2 weeks, take 6 sets (6 venepunctures, 12 bottles).
  • Ideally these are spaced over 24 hours, but if sepsis suspected, they may be taken at the same time from several sites.
  • If the patient is in septic shock, do not delay antibiotics if multiple cultures are difficult to obtain.
  • Ensure good technique and label each bottle clearly with the specific site it came from.

  • non-immunosuppressed sepsis without apparent source.
  • immunosuppressed sepsis without apparent source.
  • if there is a focus, see specific guideline e.g. urinary tract infection, meningitis, cholecystitis/cholangitis.
  • after surgery, see Sepsis (Post-operative).
  • after transrectal ultrasound-guided prostate biopsy, see Post-TRUS sepsis.
• Review recent microbiology results including any reported antimicrobial resistance. See guidance below for those colonised with extended-spectrum beta-lactamase (ESBL) producing gram-negatives in the past 12 months. See also separate MRSA guidelines.

Pathogens

• Common: S. aureus, and Gram-negative bacteria, especially E. coli.
• Once pathogens are known, change antimicrobial therapy according to susceptibilities.

Drug treatment

• Duration: depends on organism, site of infection, and adequate source control. Consultation with Infectious Diseases for S. aureus bacteraemia, endocarditis, and other complex conditions is essential.

Non-immunosuppressed sepsis without apparent source

If there are risk factors for immunosuppression, see immunosuppressed sepsis without apparent source.

Non-immunosuppressed sepsis without apparent source is divided into three sections:

• community-acquired
• healthcare-associated
• ESBL-colonised in the past 12 months

Community-acquired

ceftriaxone HMLSchedNZFPMLnoids Ceftriaxone F: n/a Half life: 8 hours Elimination: 50% renal and 50% biliary excretion fe: 0.5

IV 2 g every 24 hours

• If MRSA-colonised, add vancomycin – See guideline (dose at the upper end of the range).
• fe = 0.5

If patient has hypotension and/or new organ dysfunction (two options based on CrCl):

CrCl ≥ 20 mL/min, ADD:

gentamicin HMLSchedNZFPMLnoids Gentamicin F: n/a Half life: 3 hours Elimination: renal fe: 0.9 Additional points: TDM.

Single dose of IV 7 mg/kg ideal body weight. Round dose down to nearest half vial (40 mg). Consult Infectious Diseases/Clinical Microbiology before giving a second dose. See dosing/monitoring guidelines.

• Aim to stop gentamicin after the first dose and use alternative active agents where able. If in doubt consult Infectious Diseases/Clinical Microbiology.
• fe = 0.9. Consult pharmacist for dosing advice if subsequent doses are to be given.

OR

CrCl < 20 mL, use monotherapy of:

piperacillin+tazobactam HMLNZFPMLnoids Piperacillin+Tazobactam F: n/a Half life: 1 hour Elimination: renal fe: 0.8/0.6

IV 4 g/500 mg every twelve hours

• If MRSA-colonised, consult Infectious Diseases/Clinical Microbiology
• If still on piperacillin+tazobactam beyond 48 hours, consider measuring a trough concentration. Consult Infectious Diseases for interpretation.
• fe (piperacillin) = 0.8, fe (tazobactam) = 0.6

Severe penicillin allergy

meropenem HMLNZFPMLnoids Meropenem F: n/a Half life: 1 hour Elimination: renal; hydrolysis fe: 0.7

IV 1 g every eight hours

• Meropenem may be used in severe penicillin allergy (< 1% cross reactivity). Consult Infectious Diseases for severe cephalosporin allergy.
• Meropenem rapidly and significantly reduces sodium valproate concentrations. Concomitant administration may precipitate seizures in patients with a pre-existing seizure disorder. Discuss alternative antibiotic options with Infectious Diseases/Clinical Microbiology.
• If still on meropenem beyond 48 hours, consider measuring a trough concentration. Consult Infectious Diseases for interpretation.
• fe = 0.7, start with full dose initially then consider extending dose interval and/or decreasing dose for subsequent doses if CrCl is reduced (< 30 mL/min). Consult pharmacist.

Healthcare-associated

• If MRSA-colonised, add vancomycin – See guideline (dose at the upper end of the range).
• fe = 0.5

If patient has hypotension and/or new organ dysfunction (two options based on CrCl):

CrCl ≥ 20 mL/min, ADD:

• Aim to stop gentamicin after the first dose and use alternative active agents where able. If in doubt consult Infectious Diseases/Clinical Microbiology.
• fe = 0.9. Consult pharmacist for dosing advice if subsequent doses are to be given.

OR

CrCl < 20 mL, use monotherapy of:

• If MRSA-colonised, consult Infectious Diseases/Clinical Microbiology
• If still on piperacillin+tazobactam beyond 48 hours, consider measuring a trough concentration. Consult Infectious Diseases for interpretation.
• fe (piperacillin) = 0.8, fe (tazobactam) = 0.6

Severe penicillin allergy

• Meropenem may be used in severe penicillin allergy (< 1% cross reactivity). Consult Infectious Diseases for severe cephalosporin allergy.
• Meropenem rapidly and significantly reduces sodium valproate concentrations. Concomitant administration may precipitate seizures in patients with a pre-existing seizure disorder. Discuss alternative antibiotic options with Infectious Diseases/Clinical Microbiology.
• If still on meropenem beyond 48 hours, consider measuring a trough concentration. Consult Infectious Diseases for interpretation.
• fe = 0.7, start with full dose initially then consider extending dose interval and/or decreasing dose for subsequent doses if CrCl is reduced (< 30 mL/min). Consult pharmacist.

ESBL-colonised in past 12 months

• Meropenem may be used in mild or severe penicillin allergy (< 1% cross reactivity). Consult Infectious Diseases for severe cephalosporin allergy.
• Meropenem rapidly and significantly reduces sodium valproate concentrations. Concomitant administration may precipitate seizures in patients with a pre-existing seizure disorder. Discuss alternative antibiotic options with Infectious Diseases/Clinical Microbiology.
• If still on meropenem beyond 48 hours, consider measuring a trough concentration. Consult Infectious Diseases for interpretation.
• fe = 0.7, start with full dose initially then consider extending dose interval and/or decreasing dose for subsequent doses if CrCl is reduced (< 30 mL/min). Consult pharmacist.

Immunosuppressed sepsis without apparent source

If there are no risk factors for immunosuppression, see non-immunosuppressed sepsis without apparent source.

If ESBL-colonised in past 12 months, see separate guideline.

• If MRSA-colonised, consult Infectious Diseases/Clinical Microbiology.
• If still on piperacillin+tazobactam beyond 48 hours, consider measuring a trough concentration. Consult Infectious Diseases for interpretation.
• fe (piperacillin) = 0.8, fe (tazobactam) = 0.6, start with full dose initially and consider extending dose interval if CrCl is reduced (< 40 mL/min). Consult pharmacist.

If patient has hypotension and/or new organ dysfunction, ADD:

• Aim to stop gentamicin after the first dose and use alternative active agents where able. If in doubt consult Infectious Diseases/Clinical Microbiology.
• fe = 0.9. Consult pharmacist for dosing advice if subsequent doses are to be given.

Mild penicillin allergy

• If intra-abdominal source is possible, add metronidazole IV 500 mg every 12 hours to cefepime (with/without gentamicin).

cefepime HMLNZFPMLnoids Cefepime F: n/a Half life: 2 hours Elimination: renal fe: 0.8

IV 2 g every eight hours

• fe = 0.8, start with full dose initially, then consider extending dose interval and/or decreasing dose for subsequent doses if CrCl is reduced (< 40 mL/min). Consult pharmacist.

If patient has hypotension and/or new organ dysfunction, ADD:

• Aim to stop gentamicin after the first dose and use alternative active agents where able. If in doubt consult Infectious Diseases/Clinical Microbiology.
• fe = 0.9. Consult pharmacist for dosing advice if subsequent doses are to be given.

Severe penicillin allergy

• Meropenem may be used in severe penicillin allergy (< 1% cross reactivity). Consult Infectious Diseases for severe cephalosporin allergy.
• Meropenem rapidly and significantly reduces sodium valproate concentrations. Concomitant administration may precipitate seizures in patients with a pre-existing seizure disorder. Discuss alternative antibiotic options with Infectious Diseases/Clinical Microbiology.
• If still on meropenem beyond 48 hours, consider measuring a trough concentration. Consult Infectious Diseases for interpretation.
• fe = 0.7, start with full dose initially then consider extending dose interval and/or decreasing dose for subsequent doses if CrCl is reduced (< 30 mL/min). Consult pharmacist.

Topic Code: 99250

must be prescribed or recommended by a consultant.