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Table 2 Recent studies (from 1995 to 2005) reporting data on polymyxin-induced toxicity in patients without cystic fibrosis

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     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
  1. 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.