From: Toxicity of polymyxins: a systematic review of the evidence from old and recent studies
 | 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 | Â | Â | Â | Edematous eczema |
2 | 1998 [58] | Department of dermatology | Colistimethate sodium (ophthalmic solution) | 1 | 4 year old male with bilateral ocular prosthesis | Â | Â | Â | Â | 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 | Â | No adverse reactions | Â | Â |
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 | Â | No nephrotoxicity | Â | No hematological toxicity |
6 | 2002 [74] | Neurosurgical wards | Colistimethate sodium (IV) | 1 | 14 year old male | 1 MIU q6h for 30 days | Â | No adverse reactions | Â | Â |
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) | Â |
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 | Â |
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) | Â | Â |
11 | 2004 [75] | ICU | Colistimethate sodium (IV) | 1 | 41 year old male | 2 MIU/day continuous infusion | Â | No adverse reactions | Â | Â |
12 | 2004 [76] | ICU | Colistimethate sodium (IV) | 1 | 48 year old male | 9 MIU/day (2.5 mg/kg/day) for 15 days | Â | No adverse reactions | Â | Â |
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 | Â |
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 | Â |
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 | Â | Worsening of renal function: 1 pt | No neurotoxicity | Â |
19 | 2005 [79] | ICU | Colistimethate sodium (IV) | 1 | 57 year old male | 250 mg q6h for 4 days | Â | Acute renal failure (on the 4th day of colistin therapy) | Â | Â |
20 | 2005 [80] | Neurosurgical wards | Colistimethate sodium (intraventricular) | 1 | 23 year old female | 125,000 IU q12h for 3 weeks | Â | No adverse reactions | Â | Â |
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 | Â | 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 | Â | Â |
23 | 2005 [83] | ICU | Colistimethate sodium (IV) | 14 | Mean age: 49 years | Mean dose: 6 MIU/day. Mean duration: 12 days | Â | 1 pt experienced deterioration of renal function (serum creatinine up to 2.8 mg/dl) | Â | Â |
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 |