Microbiologic Cure with a Simplified Dosage of Intravenous Colistin in Adults: A Retrospective Cohort Study

Figures & data

Figure 1 Colistin-meropenem combination mechanism of action. The cationic colistin binds to anionic lipopolysaccharide molecules by displacing calcium and magnesium from the outer membrane of Gram-negative bacilli, resulting in altered permeability of the bacteria’s membrane.

Note: Adapted from Journal of Infection, 69/1, Martis N, Leroy S, Blanc V, Colistin in multi-drug resistant Pseudomonas aeruginosa blood-stream infections: a narrative review for the clinician, 1-12, Copyright 2014, with permission from Elsevier.⁵

Abbreviation: PBP, penicillin binding protein.

Table 1 The Simplified Fixed-Dose Regimen of IV Colistimethate Sodium in Adults

CrCl	Weight^a	Dose
≥ 50	< 60 kg	2 MIU q8h
	60 −90 kg	2.5 MIU q8h
	> 90 kg	3 MIU q8h
30–49	< 60 kg	2.25 MIU q12h
	60 −90 kg	2.5 MIU q12h
	> 90 kg	2.75 MIU q12h
10–29	< 60 kg	1.75 MIU q12h
	60 −90 kg	2 MIU q12h
	> 90 kg	2.25 MIU q12h
< 10	Any	1.75 MIU q12h
CRRT	Same as CrCl 30–49
HD	Any	1.25 MIU q12h, schedule post HD on HD days
PD	< 60 kg	1.5 MIU q72h
	60 −90 kg	2 MIU q72h
	> 90 kg	2.5 MIU q72h

Note: ^aActual body weight was used.

Abbreviations: CrCl, creatinine clearance (mL/minute); CRRT, continuous renal replacement therapy; HD, hemodialysis; IV, intravenous; MIU, million international units; PD, peritoneal dialysis.

Table 2 Baseline Characteristics

Variable	SFDR Group (n=42)	WBD Group (n=42)	p value^a
Age (years), mean (SD)^b	64 (18)	62 (22)	0.740
SOFA score, median (Q1, Q3)^c	4 (4, 6)	5 (5, 9)	0.078
Male, counts (%)^d	28 (67%)	32 (76%)	0.334
Weight (kg), mean (SD)^b	77 (19)	72 (21)	0.268
BMI (kg/m^2), mean (SD)^b	27 (7)	30 (8)	0.194
Pre-existing conditions, counts (%)^d
Diabetes	17 (41%)	24 (57%)	0.127
Hypertension	29 (69%)	26 (62%)	0.491
Ischemic heart disease	8 (19%)	12 (29%)	0.306
Heart failure	12 (29%)	10 (23%)	0.620
Stroke history	8 (19%)	5 (12%)	0.366
Lung disease	14 (33%)	9 (21%)	0.221
Malignancy	15 (36%)	1 (2.4%)	<0.001
HD	5 (12%)	8 (19%)	0.366
Initial lab data
WBC (10^9/L), mean (SD)^b	11.4 (6.9)	10.1 (3.5)	0.371
Hemoglobin (g/dL), mean (SD)^b	9.6 (1.8)	9.6 (1.9)	0.993
Platelets (10^9/L), median (Q1, Q3)^c	255 (150, 374)	341 (220, 440)	0.064
PT INR, mean (SD)^b	1.16 (0.25)	1.18 (0.29)	0.853
SrCr (mg/dL), median (Q1, Q3)^c,e,f	0.6 (0.4, 1.1)	0.8 (0.45, 1.55)	0.211
CrCl (mL/min), mean (SD)^b,e,f	77 (36)	70 (40)	0.402
Serum bicarbonate (mEq/L), mean (SD)^b	28 (4)	26 (4)	0.157
Lactic acid (mmol/L), mean (SD)^b	1.3 (0.5)	1.6 (0.8)	0.113
Total bilirubin (mg/dL), median (Q1, Q3)^c	0.5 (0.3, 1)	0.7 (0.35, 0.9)	0.484
Bacterial isolate, counts (%)^d
Pseudomonas aeruginosa	21 (50%)	20 (47.6%)	0.827
Acinetobacter baumannii	13 (31%)	15 (35.7%)	0.214
Klebsiella pneumoniae	7 (16.7%)	4 (9.5%)	0.942
Escherichia coli	1 (2.4%)	2 (4.8%)	0.557
Morganella morganii	0	1 (2.4%)	N/A
Colistin MIC (µg/mL), mean (SD)^b	0.82 (0.57)	0.69 (0.43)	0.421
Culture site, counts (%)^d
Lower respiratory tract	22 (52.4%)	28 (66.7%)	0.182
Urine	12 (28.6%)	7 (16.7%)	0.192
Tissue/wound	5 (11.9%)	7 (16.7%)	0.389
Blood	3 (7.1%)	0	N/A
CoVID-19 coinfection, counts (%)^d	1 (2.4%)	0	N/A
Type of ICU, counts (%)^d
Medical	22 (52%)	24 (57%)	0.661
Surgical	13 (31%)	8 (19%)	0.208
Cardiovascular	7 (17%)	10 (24%)	0.415

Notes: ^aA significance level of 0.05 was used. ^bT-test was used. ^cMann–Whitney U-test was used. ^dChi-square test was used. ^eHD was the only method of renal replacement therapy used in the studied patients. ^fSrCr values for patients on HD were excluded.

Abbreviations: BMI, body mass index; CoVID-19, coronavirus disease of 2019; CrCl, creatinine clearance; HD, hemodialysis; ICU, intensive care unit; SFDR, simplified fixed-dose regimen; SOFA, Sequential Organ Failure Assessment; SrCr, serum creatinine; WBC, white blood cells; WBD, weight-based dosing.

Figure 2 Patient allocation.

Abbreviations: SFDR, simplified fixed-dose regimen; WBD, weight-based dosing.

Figure 3 Forest plot for multiple logistic regression of baseline patient characteristics with microbiologic failure.

Abbreviations: BMI, body mass index; CI, confidence interval; DM, diabetes mellitus; Hgb, hemoglobin; IHD; ischemic heart disease; OR, odds ratio; SOFA, Sequential Organ Failure Assessment; SrCr, serum creatinine; WBC, white blood cells.

Table 3 Colistin Antibiotic Therapy Prescribed to the Studied Patients

Variable	SFDR Group (n=42)	WBD Group (n=42)	p value^a
Duration (days), median (Q1, Q3)^b	9.5 (7, 13)	9 (7, 13)	0.741
Single dose (MIU)			0.010
Median (Q1, Q3)^b	2 (2, 2.5)	2 (1, 2.5)
Range (IR)	1.5–3 (0.5)	0.5–5 (1.5)
The average daily dose (MIU), median (Q1, Q3)^b	6 (6, 7.5)	3 (2, 6)	<0.001
Total dose per course (MIU), mean (SD)^c	62 (30)	46 (35)	0.014
Dose frequency, n (%)^d			<0.001
Q8h	34 (81%)	18 (43%)
Q12h	7 (17%)	19 (45%)
≥Q24h	1 (2%)	5 (12%)
Concurrent carbapenem, n (%)^d			0.048
Meropenem	28 (67%)	19 (45%)
Imipenem	14 (33%)	23 (55%)
Concurrent inhaled colistin, n (%)^d	8 (19%)	8 (19%)	1.000

Notes: ^aA significance level of 0.05 was used. ^bMann–Whitney U-test was used. ^cT-test was used. ^dChi-square test was used.

Abbreviations: IR, interquartile range; MIU, million international units; SFDR, simplified fixed dose regimen; WBD, weight-based dosing.

Table 4 Endpoints Outcomes of the Study

Endpoint	SFDR Group	WBD Group	p value^a
Microbiologic cure rate, % (n/total)	69% (29/42)	36% (15/42)	0.002
Infection recurrence rate, % (n/total)^b	14% (4/29)	40% (6/15)	0.049
AKI rate, % (n/total)^c	19% (7/36)	46% (15/33)	0.021

Notes: ^aChi-square test with a significance level of 0.05 was used. ^bOnly patients who had microbiologic cure were included. ^cPatients on hemodialysis were excluded from the AKI analysis. Hemodialysis was the only method of renal replacement therapy used in the studied patients.

Abbreviations: AKI, acute kidney injury; SFDR, simplified fixed-dose regimen; WBD, weight-based dosing.

Martis N, Leroy S, Blanc V. Colistin in multi-drug resistant Pseudomonas aeruginosa blood-stream infections: a narrative review for the clinician. J Infect. 2014;69(1):1–12. doi:10.1016/j.jinf.2014.03.001

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