TABLE 4.

Step-by-step guide for empiric colistin use.

Risk assessment and management	Guidance	Additional information
Step 1: Determine unit epidemiology	-Consult Microbiologist for unit antibiogram – should be updated at a minimum annually	-Consider empiric use only in units with high prevalence of carbapenem resistant Enterobacterales (CRE), XDR A. baumannii or XDR P. aeruginosa OR in an outbreak setting
Step 2: Clinical suspicion	Clinical signs and symptoms of sepsis† in a patient admitted to hospital ≥ 48 h with rapid clinical deterioration
Step 3: Laboratory Work-up	Blood cultures
	PLUS cerebrospinal fluid (CSF): - all neonates - older children with signs and symptoms of meningitis	If it can be safely collected
	+ Inflammatory markers (CRP or PCT)	As per usual practice in the unit
	+ Specimens from suspected site of sepsis	Specimens from suspected site of sepsis which may include: catheter tip, urine, fluid/tissue, tracheal aspirate for microscopy, culture and susceptibility testing (MC&S)
Baseline renal function	Do not delay initiation of colistin while awaiting results
Step 4: Initial administration of colistin	Loading dose – 4 mg – 5 mg CBA/kg (150 000 IU/kg)
	Followed by maintenance dose 2.5 mg CBA/kg (74 000 IU/kg)	Approximately 12 h after L/D
	Empiric colistin should be given in addition to a 2nd GNB active agent depending on local antibiogram data	Consult Microbiologist/antimicrobial stewardship pharmacist to provide local antibiogram
Step 5: Clinical Review 12–24 h after colistin initiation	If biomarkers low – repeat biomarkers – if still low, consider early cessation of colistin	Ensure adequate source control – imaging to assess for collections in the abdomen, brain, chest, remove central venous catheters, bone scans
	Biomarkers high – continue therapy
Step 6: Follow up culture results and determine duration of therapy	Culture positive: switch to targeted therapy Culture negative + elevated biomarkers + rapid response to treatment – complete 5–7 days and stop if patient clinically stable	If CSF suggestive of meningitis, but cultures negative – discuss with Infectious diseases specialist/microbiologist
	Culture negative + low biomarkers + patient clinically unstable: Discuss management with infectious diseases specialist/microbiologist -Repeat blood culture/cultures from suspected site of sepsis -Check if source control was achieved -Look for alternate cause – consider early cessation of colistin at 48–72 h	Discuss with infectious diseases specialist

XDR, extensively drug resistant; CRP, C-reactive protein; PCT, procalcitonin.

^†, As per standard definitions of the term.⁴⁰