Table 2

Recent studies (from 1995 to 2005) reporting data on polymyxin-induced toxicity in patients without cystic fibrosis

Year [ref]
 Setting
 Medication used
 Number. of patients
 Demographics
 Dosage of colistin/duration
 Definition of nephrotoxicity
 Nephrotoxicity
 Neurotoxicity
 Other toxicities
1
 1995 [57]
 Department of dermatology
 Colistin sulfate (ointment/topically)
 1
 45 year old
 50,000 IU for 10 days


Edematous eczema
2
 1998 [58]
 Department of dermatology
 Colistimethate sodium (ophthalmic solution)
 1
 4 year old male with bilateral ocular prosthesis



After 3 weeks he developed itchy erythematous eruptions on both periorbital areas
3
 1999 [72]
 Neurosurgical wards
 Colistimethate sodium (intraventricular)
 2
 16 year old male and 34 year old female
 Case 1: 5 mg (62,500 IU) q12h for 19 days Case 2: 5 mg (62,500 IU) q12h for 5 days then 10 mg (125,000 IU) q12h for 12 days
No adverse reactions

4
 1999 [8]
 ICU (52%), transplant unit (13%), surgical and medical wards (35%)
 Colistimethate sodium (IV)
 59 (60 cases)
 Mean age: 42.1 years. Mean (± SD) APACHE II: 13.1 (± 7.0)
 Mean duration: 12.6 d (2 to 34 d). Mean daily dose: 152.8 mg (approximately 2 MIU) (60–300 mg)
22 pts (37%; 11/41 with normal baseline renal function had worsening during treatment (mean increase in serum creatinine 0.9 ± 0.6 mg/dl) and 11/19 with abnormal baseline renal function had worsening during treatment (mean increase in serum creatinine 1.5 ± 1.4 mg/dl)). Nephrotoxicity did not cause discontinuation
 No neuromuscular disorders
5
 2000 [73]
 Medical wards
 Colistimethate sodium (aerosol)
 3
 67 year old male, 45 year old male, 59 year old male
 150 mg (2 MIU) q12h for 13 days, 100 mg (approximately 1.5 MIU) q12h for 14 days, 150 mg (2 MIU) q12h for 11 days
No nephrotoxicity
No hematological toxicity
6
 2002 [74]
 Neurosurgical wards
 Colistimethate sodium (IV)
 1
 14 year old male
 1 MIU q6h for 30 days
No adverse reactions

7
 2003 [10]
 Abdominal organ transplantation ICU
 Colistimethate sodium (IV)
 23 (20 had received organ transplantation, 3 abdominal surgery)
 Mean age: 52 years
 Mean duration: 17 days (7 to 36 days)
 Renal failure was defined by a requirement either for intermittent hemodialysis or for continuous venous hemofiltration
 1/2 pts developed renal failure requiring artificial kidney support (the other 21 pts were already receiving artificial kidney support)
 1 pt diffuse muscular weakness (resolved after discontinuation)
8
 2003 [11]
 ICU
 Colistimethate sodium (IV)
 24 with sepsis, 26 courses of colistin
 Mean age: 44.3 years. Mean APACHE II: 20.6
 Mean duration: 13.5 days (4 to 24 days). Dosage: 3 MIU q8h
 Renal failure was defined as an increase in serum creatinine >1 mg/dl during treatment
 3 pts (14.3%). Only 1 pt required continuous venovenous hemodiafiltration
 No clinically apparent neuromuscular transmission blockade
9
 2003 [36]
 Tertiary care hospital
 Polymyxin B (parenterally)
 60 receiving polymyxin B
 Mean age: 61 years
 Mean duration: 13.5 days (1 to 56 days). Mean daily dose: 1.1 MIU
 Renal failure was defined as doubling of serum creatinine value of ≥ 2.0 mg/dl
 7/50 pts (14%)

10
 2003 [74]
 ICU
 Colistimethate sodium (IV)
 35 (21 received colistin (CO group) and 14 imipenem (IM group))
 Mean age: CO group 56.9 years, IM group 64.5 years. Mean APACHE II: CO group 19.6, IM group 20.5
 CO group: mean duration 14,7 days (10 to 21 days). Dosage: 2.5 to 5 mg/kg/day
 In patients with normal renal function (creatinine <1.2), renal failure was defined as creatinine value >2 mg/dl, as a reduction of creatinine clearance of 50% relative to antibiotic initiation, or need for renal replacement therapy. In patients with normal renal function, renal failure was defined as increase of 50% of the baseline creatinine level, as a reduction of creatinine clearance of 50% relative to antibiotic initiation, or need for renal replacement therapy
 5/21 pts (24%; CO group), 6/14 pts (42%; IM group)

11
 2004 [75]
 ICU
 Colistimethate sodium (IV)
 1
 41 year old male
 2 MIU/day continuous infusion
No adverse reactions

12
 2004 [76]
 ICU
 Colistimethate sodium (IV)
 1
 48 year old male
 9 MIU/day (2.5 mg/kg/day) for 15 days
No adverse reactions

13
 2004 [37]
 Tertiary care hospital, ICU (92%)
 Polymyxin B (IV)
 25 (29 courses: 21 IV, 6 aerosol, 2 combination)
 Mean age: 55 years. Mean APACHE II: 21
 Loading dose on day 1 with 2.5 to 3 mg/kg IV polymyxin B. Aerosolized: approximately 2.5 mg/kg/day (approximately 1.75 MIU). Mean duration: 19 d (2 to 57 d)
 Nephrotoxicity was defined as the doubling of serum creatinine during therapy
 3/29 courses (10%)
 2/29 courses (7%) onset of seizures and neuromuscular weakness possibly related to polymyxin B
14
 2005 [12]
 ICU
 Colistimethate sodium (IV)
 43
 Mean age: 56.5 years. APACHE II: 25.8 ± 3.7
 3 MIU q8h
 Acute renal failure was defined as a rise of ≥ 2 mg/dl in serum creatinine level in patients with previously normal renal function. In patients with a history of renal insufficiency, acute on chronic renal failure was defined as at least doubling of the baseline serum creatinine level (defined as the creatinine level at the initiation of colistin treatment)
 8/43 pts (18.6%; 3/35 pts with normal renal function (8.6%) and 5/8 pts with chronic renal failure (62.5%))
 No paresthesias, vertigo, muscle weakness, or apnea were observed
15
 2005 [77]
 ICU (84%), medical (11%), surgical (5%)
 Colistimethate sodium (aerosol, IV, IM, intrathecal)
 80 (85 courses: 71 aerosol, 12 IV or IM, 2 intrathecal)
 Mean age: 57 ± 15 years
 Mean duration of aerosol: 12 ± 8 d. Mean duration of IV or IM: 11 ± 6 d. Mean duration of intrathecal: 8 d and 10 d
 Nephrotoxicity was defined as a serum creatinine increase of 50% or 1 mg/dl with respect to the baseline level during treatment
 12 courses of IV or IM were recorded. Mean ± SD baseline serum creatinine: 1.25 ± 0.79 mg/dl. Mean ± SD final serum creatinine: 1.20 ± 0.64 mg/dl. Mean ± SD baseline BUN: 8.95 ± 8.96 μmol/l. Mean ± SD final BUN: 8.39 ± 8.06 μmol/l

16
 2005 [38]
 Mainly ICU pts
 Colistimethate sodium (IV)
 17 (19 courses)
 Median age: 51 years. Median APACHE II: 14
 Mean ± SD duration: 43.4 ± 14.6 days. Mean ± SD daily dose: 4.4 MIU (352 mg) ± 2.1 MIU (168 mg)
 Renal failure was defined as an increase more than 50% of the baseline creatinine level to a value higher than 1.3 mg/dl or as a decline in renal function requiring renal replacement therapy
 Median baseline serum creatinine: 0.6 mg/dl. Slight increase of the median of values of creatinine at the end by 0.1 mg/dl. Median baseline BUN: 42 mg/dl. Median final BUN: 41 mg/dl. 1 pt had an increase of more than 50% of the baseline creatinine level to a value higher than 1.3 mg/dl at the end of colistin treatment
 No apnea or other evidence of neuromuscular blockade. 1 pt polyneuropathy (improved after the end of colistin treatment)
 No hepatobiliary toxicity
17
 2005 [35]
 ICU (80%), medical and surgical wards (20%)
 Colistimethate sodium (IV)
 50 (54 episodes)
 Mean age: 59.2 years. Mean APACHE II: 16.1
 Mean duration: 21.5 days. Mean daily dose: 4.5 MIU
 Renal failure was defined as an increase more than 50% of the baseline creatinine level to a value higher than 1.3 mg/dl or as a decline in renal function requiring renal replacement therapy
 4/50 pts (8%)
 1 pt polyneuropathy (not confirmed) resolved without discontinuation
18
 2005 [78]
 ICU
 Colistimethate sodium (aerosol)
 8
 Mean age: 59.6 years. Mean APACHE II: 14.6
 Dosage (range): 1.5 to 6 MIU/day. Duration (mean): 10.5 days
Worsening of renal function: 1 pt
 No neurotoxicity
19
 2005 [79]
 ICU
 Colistimethate sodium (IV)
 1
 57 year old male
 250 mg q6h for 4 days
Acute renal failure (on the 4th day of colistin therapy)

20
 2005 [80]
 Neurosurgical wards
 Colistimethate sodium (intraventricular)
 1
 23 year old female
 125,000 IU q12h for 3 weeks
No adverse reactions

21
 2005 [81]
 ICU
 Colistimethate sodium (IV)
 55
 Mean age: 40 ± 16 years. Mean APACHE II: 21 ± 7
 Duration (mean): 13 ± 5 days
 Renal failure was defined as a serum creatinine value of 2 mg/dl or higher, as a reduction in creatinine clearance of 50% compared to therapy initiation, or as a decline in renal function that prompted renal replacement therapy
 No adverse reactions. Mean creatinine levels before treatment: 2.3 ± 0.5 mg/dl. Mean creatinine levels after treatment: 2.5 ± 0.6 mg/dl

22
 2005 [82]
 ICU
 Colistin (IV)
 1
 35 year old male
 6 MIU/day for 12 days, 3 days, and 1 day
Acute renal failure occurred at the 2nd and 3rd introduction of colistin. Renal function returned to normal values within 3 and 5 days after colistin withdrawal

23
 2005 [83]
 ICU
 Colistimethate sodium (IV)
 14
 Mean age: 49 years
 Mean dose: 6 MIU/day. Mean duration: 12 days
1 pt experienced deterioration of renal function (serum creatinine up to 2.8 mg/dl)

24
 2005 [84]
 ICU, medical wards
 Colistimethate sodium (aerosol)
 21
 Mean age: 60.6 ± 15 years. Mean APACHE II: 23.1 ± 9.1
 19 pts received 2 MIU/day, 1 pt 3 MIU/day, and another pt 4 MIU/day. Median duration: 14 days
 Renal failure was defined as a decrease in the estimated creatinine clearance rate of 50%, compared with the rate at the start of therapy, or a decline in renal function that necessitated renal replacement therapy
 No episodes of acute renal failure
 No symptoms of neurotoxicity
 1 pt experienced bronchospasm that resolved on discontinuation of colistin therapy

BUN, blood urea nitrogen; ICU, intensive care unit; IM, intramuscularly; IV, intravenously; MIU, million international units; Pt(s), patient(s); ref, reference; SD, standard deviation.

Falagas and Kasiakou Critical Care 2006 10:R27   doi:10.1186/cc3995

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