Inappropriate Doses of Intravenous Polymyxin B after Renal Adjustment Lead to Treatment Failure

Ismail, Bahiah; Shafei, Mohd Nazri; Harun, Azian; Ali, Saedah; Omar, Mahamarowi; Deris, Zakuan Zainy

doi:10.1590/s2175-97902020000119036

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Brazilian Journal of Pharmaceutical Sciences

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Article • Braz. J. Pharm. Sci. 57 • 2021 • https://doi.org/10.1590/s2175-97902020000119036 copy

Inappropriate Doses of Intravenous Polymyxin B after Renal Adjustment Lead to Treatment Failure

Authorship SCIMAGO INSTITUTIONS RANKINGS

Sub-therapeutic doses, shorter duration of therapy, female gender, bacteremia, and renal impairment were among independent predictors of polymyxin B treatment failure. In this study, we found an association between inappropriate doses of polymyxin B (<15000 or >25000 unit/kg/day) and renal impairment. Inappropriate doses of polymyxin B were significantly associated with CrCl 20-50 mL/min (p = 0.021, ORadj 6.660, 95% CI 1.326, 33.453) and CrCl <20 mL/min (p = 0.001, ORadj 22.200, 95% CI 3.481, 141.592). By conducting sub-group analysis only using subjects with appropriate dosage, renal impairment was not associated with polymyxin B treatment failure, thus indicating that treatment failure was due to an inappropriate dose of polymyxin B, rather than renal impairment. In conclusion, renal impairment was not directly associated with treatment failure but was due to an inappropriate dosage of polymyxin B after renal adjustment

Keywords:
Polymyxin B; Sub-therapeutic dose; Renal impairment; Treatment failure

	Appropriate dose (n=66)	Inappropriate Dose (n=18)	Single logistic regression			Multiple logistic regression^†
Variables	No (%) or Mean (SD)	No (%) or Mean (SD)	OR (95% CI)	p value	OR (95% CI)	p value
Age (Year)*	50.0 (18.9)	60.6 (14.1)	1.04 (1.00, 1.08)	0.041
Body weight ≥ 80kg < 80kg	9 (13.4) 58 (86.6)	2 (11.8) 15 (88.2)	0.859 (0.168, 4.403)	0.856
Gender Male Female	46 (68.7) 21 (31.3)	13 (76.5) 4 (23.5)	1.48 (0.43, 5.09)	0.531
Creatinine Clearance (mL/min)*	58.4 (33.8)	29.8 (21.1)	0.953 (0.925, 0.983)	0.002
Renal impairment severity - CrCl ≥50 mL/min - CrCl 20-50 mL/min - CrCl <20 mL/min	37 (55.2) 25 (37.3) 5 (7.5)	2 (11.8) 9 (52.9) 6 (35.3)	1.00 6.660 (1.326, 33.453) 22.200 (3.481, 141.592)	0.005 0.021 0.001	1.00 6.660 (1.326, 33.453) 22.200 (3.481, 141.592)	0.005 0.021 0.001
Type of infection - Bacteremia - Pneumonia	31(46.3) 36 (53.7)	8 (47,1) 9 (52.9)	1.032 (0.355, 2.999)	0.953
Organism - Acinetobacter - Mixed Acinetobacter or other organism	59 (88.1) 8 (11.9)	15 (88.2) 2 (11.8)	1.017 (0.195, 5.295)	0.984

Variables	Treatment Success (n=46)	Treatment Failure (n=20)	Single logistic regression p value
Variables	No (%) or Mean (SD)	No (%) or Mean (SD)	Single logistic regression p value
Demographic data
Age (year)*	48.4 (19.6)	53.8 (17.8)	0.291
Body Weight (kg)*	64.8 (12.2)	61.3 (11.2)	0.261
Gender
Male	36 (78.3)	10 (50.0)	0.025
Female	10 (21.7)	10 (50.0)
Patient admitted from	11 (23.9)	1 (5.0)	0.300
- Emergency Department	13 (23.8)	7 (35.0)	0.384
- Operation theaters	7 (15.2)	2 (10.0)	0.346
- Other ICU/HDU	15 (32.6)	10 (50.0)	0.495
- Other wards
APACHE II Score*	27.2 (4.2)	28.5 (3.3)	0.205
Baseline creatinine clearance (mL/min)*	62.4 (33.6)	48.7 (33.8)	0.137
Days of ventilation before need polymyxin B therapy*	14.7 (11.2)	13.9 (11.4)	0.771
Type of infection
- Bacteremia	17 (37.0)	13 (65.0)	0.039
- Pneumonia	29 (63.0)	7 (35.0)
Organism isolated
Acinetobacter spp.	42 (91.3)	17 (85.0)	0.450
Mixed Acinetobacter infection or other organisms	4 (9.7)	3 (15.0)
Underlying diseases
Hypertension	19 (41.3)	10 (50.0)	0.514
Diabetes Mellitus	16 (38.8)	9 (45.0)	0.433
Renal impairment
- CrCl ≥50 mL/min	29 (63.0)	7 (35.0)	0.118
- CrCl 20-50 mL/min	14 (30.4)	11 (55.0)	0.312
- CrCl <20 mL/min	3 (6.5)	2 (10.0)	0.869
Ischemic heart diseases	8 (17.4)	5 (25.0)	0.477
Chronic obstructive airway diseases	4 (8.7)	1 (5.0)	0.607
Cerebral vascular diseases	5 (10.9)	0 (0.0)	0.999
Malignancy	2 (4.3)	2 (10.0)	0.389
Procedures
Planned surgery	4 (8.7)	2 (10.0)	0.866
Unscheduled/emergency surgery	25 (54.3)	11 (55.0)	0.961
Chest drains	6 (13.0)	3 (15.0)	0.832
Tracheostomy	21 (45.7)	6 (30.0)	0.238
Parenteral nutrition	16 (34.8)	9 (45.0)	0.433
Polymyxin B therapy
Day of polymyxin B initiation after sepsis*	3.83 (2.17)	4.80 (2.28)	0.146
Delay therapy >72H of sepsis symptoms	22 (47.8)	5 (25.0)	0.089
Duration of therapy (days)*	11.4 (2.9)	8.6 (3.0)	0.003
Polymyxin B regimen^#
- Combination with cefoperazone/sulbactam	34 (73.9)	9 (45.0)	0.027
- Combination with carbapenems
- Other antibiotics combination	10 (21.7)	4 (20.0)	0.874
- Monotherapy	14 (30.4)	14 (70.0)	0.004
	1 (2.2)	1 (5.0)	0.549
Deterioration of renal functions while on treatment	1 (2.2)	2 (10.0)	0.200

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] *Correspondence:
Z. Z. Deris. Department of Medical Microbiology and Parasitology. School of Medical Sciences. Universiti Sains Malaysia.