Supplemental Table 2. Dose regimens of polymyxins used in the literature.
Drug
Dose
Comments
Parenteric

US: .5–5 mg/kg (0.31–0.63 MIU/kg)/d,

Colistin can be used IM at the same doses as IV
in 2–4 doses

IM use is not common due to the severe pain caused at
(IV/IM) colistin

Europe (UK) 4–6 mg/kg (0.5–0.75
MIU/kg)/d in 3 doses


30-min infusion for 2 MIU is suggested
(package insert)

the injection site.
In literature, doses between 2-4.5 MIU were given over
9–180 min and mostly as a 15- to 60-min infusion [17]

Further adjustment of colistin dosage when there is
The manufacturers recommend different
impaired renal function, and for critically ill or
daily doses [56]
immunocompromised patients is needed according to
the manufacturer instructions, but that suboptimal
dosage may lead to resistance.

Drug absorption and clearance differ between children
and adults and adjustment for body weight is essential.
High dose

Infusion rate of 1.5 h instead of 30 min
protocol of IV
for the 9 MIU loading dose can be
colistin with
considered.
loading dose


The duration of treatment depends on the type of
infection

For all subsequent doses (2 MIU q6 h), a
Adjustments in total daily dose are needed in the
presence of AKI.
(frequently
30-min infusion and up to 720 mg (9

In obese patients, dosage should be based on IBW
used in adult
MIU)/ d (in 3 doses) for life-threatening

Recent data on population PK of i.v. colistin in critically
CF patients)
infections [56].
ill patients, suggested to apply a loading dose to obtain
In case of toxicity, evaluation of renal
more rapidly plasma concentrations above the EUCAST
function and drug interactions and a
MIC breakpoints for GNR [9, 20].

slower infusion rate of 2 MIU over 1.5 h
can be considered [12].

CF patients express high distribution volumes and halflives of drugs are shorter; as a result, high dose
regimens are needed in these patients [56]
Continuous

Infusion rate of 5-6 mg/h can be used in
administration
patients with normal renal function
of polymyxins
(package insert).


Continuous infusion PB had a higher incidence of
AKI compared with 60–90 minute infusion [14].

It remains unclear whether continuous infusion of
2 MIU per 24 h continuous infusion has
polymyxins is associated with lower rates of AKI
been used in a case report to minimize
toxicity [13].
Inhaled Colistin

for pneumonia
[14].
40 mg (0.5 MIU) q 12 h (BW⩽40 kg)
For recurrent pulmonary infections: 160 mg (2 million IU)
and 80 mg (1 MIU) q 12 h (BW >40 kg)
every 8 h [18].
For spontaneously breathing patients: 80 mg (1 million IU)
of colistin
CNS infection
(MDR-GNR)

Intrathecal use ranged from 1.6 mg
Not approved by the FDA; evidence is based on case reports;
(20,000 IU) to 20 mg (0.25 MIU)/d [15,
IV colistin may or not be given
16].
Abbreviations: AKI: Acute kidney injury, BW: body weight, CF: cystic fibrosis, d: days.
EUCAST: European Committee on Antimicrobial Susceptibility Testing, FDA: Food and Drug
Administration, GNR: gram negative rods, IBW: ideal body weight, IM: Intramuscular, IV:
intravenous, MDR: Multidrug resistant, MIU: million international units, PK: pharmacokinetic,
UK: United Kingdom, United States: US
*1
million IU (MIU) is equivalent to 30 mg of CBA. It has been reported that ∼12 500 IU CMS
is equivalent to 1 mg of CMS and that ∼2.67 mg of colistimethate sodium is equivalent to 1 mg
of colistin base. Depending on the manufacturer, it has also been reported that 1 mg of colistin
base is equivalent to 2.4 mg or 30 000 IU of CMS. In most cases description was not provided
regarding what body weight (ie, ABW vs IBW) the doses were based upon.
** The dosage of intravenous colistin recommended by the manufacturers in the United States is
2.5–5 mg/kg (31,250–62,500 IU/kg) per day, divided into 2–4 equal doses (1 mg of colistin
equals 12,500 IU). This dosage refers to adult patients with normal renal function [10]. The
dosage recommended by the manufacturers in the United Kingdom is 4–6 mg/kg (50,000–75,000
IU/kg) per day, in 3 divided doses for adults and children with body weights of ⩽60 kg and 80–
160 mg (1–2 million IU) every 8 h for those with body weights of >60 kg. When colistin is given
by inhalation, the dosage recommended by the manufacturers in the United Kingdom is 40 mg
(500, 000 IU) every 12 h for patients with body weights of ⩽40 kg and 80 mg (1 million IU)
every 12 h for patients with body weights of >40 kg. For recurrent pulmonary infections, the
dosage of aerosolized colistin can be increased to 160 mg (2 million IU) every 8 h [18].