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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.