Sepsis and Directed Therapy for Blood Stream Infections

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Development of sepsis begins with infection (tissue invasion), which can then progress to bacteraemia (blood stream involvement) and lead on to severe sepsis (infection with single organ dysfunction). Patients with severe sepsis may develop septic shock (with hypotension not responsive to fluids), and/or multi-organ dysfunction syndrome (MODS) with dysfunction of 2 or more organs. Symptoms and signs of sepsis may or may not include signs specific to a source such as cough or dysuria.

Sepsis should be considered in a child with fever who is severely ill and is likely to have infection. It is usually associated with tachycardia, tachypnoea, raised white cell count and organ dysfunction. Hypotension is a late sign of septic shock in children. Warning signs in adults include arterial hypotension (<90mmHg systolic), fever >38oC, tachycardia, tachypnoea and altered mental status. Importantly many of these signs indicate decreased organ perfusion and can be improved with careful and early fluid resuscitation, appropriate antibiotic treatment, and repeated re-assessment (at least half-hourly). Rapid treatment of sepsis saves lives.

Common causative organisms include: Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Neisseria meningitidis. Enteric Gram-negative organisms such as Escherichia coli, Klebsiella pneumoniae and Salmonella spp. are more common in children with underlying malnutrition.

Sepsis without focus

Take blood cultures then administer antibiotics within 1 hour.

Continue repeated assessment and investigation for site of infection. Refer to relevant section once a focus is found and direct antibiotics accordingly.

Antimicrobial 

Immunocompetent and low risk for multidrug resistant organisms (MDR):

Ceftriaxone 2g (child 50mg/kg) IV OD

PLUS

Gentamicin 4-5mg/kg (child 7.5mg/kg) IV OD

PLUS

Cloxacillin 2g (child 50mg/kg) IV QID

High risk for MDR or significant immunocompromise:

Ceftriaxone 2g (child 50mg/kg) IV OD

PLUS

Amikacin 28mg/kg IV OD as a first dose in patients with creatinine clearance >60ml/minute. Use 16-20mg/kg if creatinine clearance <60ml/minute. For subsequent doses see Aminoglycoside dosing section.

Child 15mg/kg IV OD.

If amikacin is not available and patient is likely to have normal renal function give Gentamicin 7mg/kg IV for first dose. If patient is likely to have abnormal renal function give Gentamicin 4-5mg/kg IV OD.

PLUS

Vancomycin 25-30mg/kg loading dose, then dose according to Vancomycin dosing section.

Do not continue gentamicin or amikacin beyond 72 hours.

Comments and Duration of Therapy 

Consider patients high risk for MDR if any of the following:

  • Recent antibiotic use
  • Recent admission to hospital
  • Known MDR colonization

If using gentamicin, amikacin or vancomycin for sepsis, daily monitoring of creatinine clearance is particularly important (refer to Cockcroft-Gault calculation).

Typhoid (enteric fever) may present as fever with few focal features. If Typhoid is suspected see Typhoid (enteric fever)- proven or suspected in Gastrointestinal Infections, for stepdown antibiotic therapy.

Septic Shock

A subset of sepsis associated with circulatory, cellular, and metabolic abnormalities. This presents as hypotension which is refractory to IV fluid replacement, requiring vasopressor therapy to maintain MAP > 65 mmHg, and associated with tissue hypoperfusion (lactate > 2 mmol / L), in the absence of hypovolaemia.

Diagnosis septic shock in patients with mean arterial pressure (MAP) < 65mmHg after adequate IV fluid replacement, or who are on vasopressors. Early administration of antibiotics is associated with improved outcomes. Patients should receive antibiotics within 1 hour of presenting with septic shock.

Refer to ICU.

Antimicrobial 

Community acquired:

Ceftriaxone 2g IV (child 50mg/kg) IV OD

PLUS

Amikacin 28mg/kg IV OD as a first dose in patients with creatinine clearance >60ml/minute. Use 16-20mg/kg if creatinine clearance <60ml/minute. For subsequent doses see Aminoglycoside dosing section.

Child 15mg/kg IV OD.

If amikacin is not available and patient is likely to have normal renal function give Gentamicin 7mg/kg IV for first dose. If patient is likely to have abnormal renal function give Gentamicin 4-5mg/kg IV OD.

PLUS

Vancomycin 25-30mg/kg loading dose, then dose according to Vancomycin dosing section.

If not improving after 48 hours and no culture results available, change to antibiotics for Hospital Acquired Septic Shock.

For dosing frequency see Aminoglycoside dosing section. Do not continue gentamicin or amikacin beyond 72 hours.

Hospital acquired:

Meropenem 1g (child 40mg/kg) IV TID

PLUS

Vancomycin 25-30mg/kg loading dose, then dose according to Vancomycin dosing section.

Comments and Duration of Therapy 

Take blood cultures then administer antibiotics within 1 hour.

Continue investigation for site of infection. Refer to relevant section once a focus is found and direct antibiotics accordingly.

Gram-negative bacteraemia

Antimicrobial 

Treat according to susceptibilities.

If site of infection is identified refer to relevant section of guideline.

Comments and Duration of Therapy 

Duration:

If site of infection remains unknown, treatment response is rapid, patient is not immunocompromised, and there is no deep-seated or uncontrolled site of infection, 5-7 days of total antibiotic treatment is adequate.

For Burkholderia pseudomallei bacteraemia see Melioidosis in Special Infections.

Staphylococcus aureus bacteraemia

General considerations

  • Where possible remove source of bacteraemia (e.g. canula, abscess, necrotic bone).
  • Evaluate clinically for metastatic foci of infection (e.g. endocarditis, septic arthritis, osteomyelitis, abscesses).
  • Repeat one set of blood cultures every 48 hours until negative.
  • Perform a transthoracic echo on all patients.

Antimicrobial

For Methicillin-sensitive Staphylococcus aureus (MSSA):

Cloxacillin 2g QID (child 50mg/kg up to 2g) (for septic shock use Q4H dosing)

For Methicillin-resistant Staphylococcus aureus (MRSA):

Vancomycin IV, dose according to Vancomycin section

Monitor creatinine every 2-3 days while patient is on vancomycin.

Comments and Duration of Therapy 

Treat as complicated if any of the following are present:

  • Positive blood culture >48 hours after starting appropriate antibiotics
  • Fever 72 hours after starting appropriate antibiotics
  • Abnormal cardiac valves
  • No source of infection identified
  • Source of infection identified but not addressed
  • Evidence of metastatic foci of infection
  • Intravascular prosthetic material

Duration:

Uncomplicated bacteraemia: Treat for 2 weeks IV.

Complicated bacteraemia: Treat for at least 4 weeks IV. Extend treatment to 6 weeks if response to antibiotics is slow.

Candidaemia

General considerations

  • Where possible remove source of candidaemia (e.g. intravenous line, catheter)
  • Evaluate clinically for metastatic foci of infection
  • Repeat one set of blood cultures every 48 hours until negative
  • Perform a transthoracic echo
  • Perform fundoscopic examination to evaluate for endophthalmitis

Antimicrobial 

Fluconazole 800mg (child 12mg/kg up to 800mg) IV for the first dose, followed by 400mg (child 6mg/kg up to 400mg) IV OD.

When clinically improved change to:

Fluconazole 400mg (child 6mg/kg) PO OD

Candida species other than C. albicans may need higher doses.

Comments and Duration of Therapy 

Metastatic complications of candidaemia include:

  • Endocarditis
  • Endophthalmitis
  • Abscesses

Duration:

No metastatic complications: Treat for 2 weeks

Metastatic complications present: Treat for 4-6 weeks

References

eTG complete. Sepsis and bacteraemia. In: Therapeutic Guidelines [digital]. Melbourne: Therapeutic Guidelines Limited; 2019. http://www.tg.org.au

Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith C, French C, et al. Surviving Sepsis Campaign Guidelines 2021. Intensive Care Med 2021; 47(11):1181-1247. doi: 10.1007/s00134-021-06506-y

Gavelli F, Castello L, Avanzi G. Management of sepsis and septic shock in the emergency department. Intern Emerg Med 2021; 16(6):1649-1661. doi: 10.1007/s11739-021-02735-7

Gusmao dos Santos C, Francis J, Guterres J, Janson S, Lopes N, Marr I, et al. HNGV Antibiotic guidelines writing group. Antibiotic guidelines Hospital Nacional Guideo Valadares. Timor-Leste; 2016